Who will inflict vengeance. That he may the better persuade believers that the persecutions which they endure will not go unpunished, he teaches that this also involves the interests of God himself, inasmuch as the same persons that persecute the pious are guilty of rebellion against God. Hence it is necessary that God should inflict vengeance upon them not merely with a view to our salvation, but also for the sake of his own glory. Farther, this expression, who will inflict vengeance, relates to Christ, for Paul intimates that this office is assigned to him by God the Father. It may be asked, however, whether it is lawful for us to desire vengeance, for Paul promises it, as though it could be lawfully desired. I answer, that it is not lawful to desire vengeance upon any one, inasmuch as we are commanded to wish well to all. Besides, although we may in a general way desire vengeance upon the wicked, yet, as we do not as yet discriminate them, we ought to desire the welfare of all. In the mean time, the ruin of the wicked may be lawfully looked forward to with desire, provided there reigns in our hearts a pure and duly regulated zeal for God, and there is no feeling of inordinate desire. Who know not. He distinguishes unbelievers by these two marks -- that they know not God, and obey not the gospel of Christ. For if obedience is not rendered to the gospel through faith, as he teaches in the first and in the last chapters of the Epistle to the Romans, [Romans 1:18ff, 16:17-19,] unbelief is the occasion of resistance to it. He charges them at the same time with ignorance of God, for a lively acquaintance with God produces of itself reverence towards him. Hence unbelief is always blind, not as though unbelievers were altogether devoid of light and intelligence, but because they have the understanding darkened in such a manner, that seeing they do not see. (Matthew 13:13.) It is not without good grounds that Christ declares that this is life eternal, to know the true God, etc. (John 17:3.) Accordingly, from the want of this salutary knowledge, there follows contempt of God, and in fine, death. On this point I have treated more fully in commenting on the first chapter of First Corinthians. [1]

Footnotes

1 - See Calvin on the Corinthians, [62]vol. 1, pp. 84-86.

In flaming fire - This is a circumstance which is not noticed in the account of his appearing in the parallel place in 1-Thessalonians 4:16. The object of the apostle here seems to be to represent him as coming amidst vivid flashes of lightning. He is commonly described as coming in clouds, and to that common description there is here added the image of incessant lightnings, as if the whole heavens were illuminated with a continued blaze.
Taking vengeance - Margin, "yielding." Greek, "giving. The word "vengeance" is used in the sense of punishment, for there cannot be in God what literally corresponds with the passion of revenge; compare the notes on Romans 12:19.
On them that know not God. - On all who are strangers to him; that is, who are living in pagan darkness, or who, having heard of him, have no practical acquaintance with him.
And that obey not the gospel of our Lord Jesus Christ. - Who do not embrace it, and practice its precepts in their lives; compare the notes on Romans 2:9.

In flaming fire - Εν φλογι πυρος· In thunder and lightning, taking vengeance - inflicting just punishment on them that know not God - the heathen who do not worship the true God, and will not acknowledge him, but worship idols; and on them that obey not the Gospel - the Jews, particularly who have rejected the Gospel, and persecuted Christ and his messengers; and all nominal Christians who, though they believe the Gospel as a revelation from God, yet do not obey it as a rule of life.

In flaming fire taking vengeance on them (6) that know not God, and that obey not the gospel of our Lord Jesus Christ:
(6) There is no knowledge of God to salvation, without the Gospel of Christ.

In flaming fire,.... Which may either refer to Christ, who will be revealed from heaven in such a manner; and whose coming will be as the lightning, not only sudden, but glorious, illustrious, and visible; he will be seen and easily discerned; there will be such a light and flaming fire about him, which, as it will serve to make him visible, will greatly add to the majesty of his appearance, and strike terror to his enemies, and burn them up round about; see Daniel 7:7 or else it may refer to the angels, who shall descend in fiery forms, which is agreeably to their nature, Psalm 104:4 and so they appeared in the forms of horses of fire, and chariots of fire, when Elijah was carried up to heaven. And it is a tradition of the Jews (z), that the angel Gabriel descended , "in a flame of fire", to burn Moses, as he was in the inn, when upon his journey from Midian to Egypt: or this clause may be read in construction with the following, as it is in the Vulgate Latin and Syriac versions, "in flaming fire taking vengeance"; and so expresses the manner in which vengeance will be taken on the wicked by Christ, the Judge of all, to whom it belongs: and the punishment of ungodly men is often signified by fire, and flames of fire, by the fire of hell, and a lake which burns with fire and brimstone, by a furnace of fire, everlasting fire, and fire that cannot be quenched, to set forth the endless torture and inconceivable misery of the damned; and it may be, some regard is had to the general conflagration, which will be at the coming of Christ, when the heavens, being on fire, shall be dissolved, the elements shall melt with fervent heat, and the earth, and all that is in it, shall be burnt up, when the bodies of the wicked, then living, will be consumed in flames of fire, and their souls feel the wrath of the Almighty. The persons who will then be punished, and on whom vengeance will be taken, are described as follows,
on them that know not God; which is a periphrasis, or common character of the Gentiles, 1-Thessalonians 4:5 who know not the one, true, and living God; or know him not so as to glorify him as God, and be thankful to him for the mercies they receive from him, and still less know him in Christ Jesus; which ignorance of theirs is not without sin, nor will it excuse from punishment; for though vengeance will not be taken on them, because they have not a spiritual saving knowledge of God, in the Mediator Jesus Christ, who never was revealed to them; yet forasmuch as they had the light and law of nature, by which the being of God, and the invisible perfections of his nature might be seen and understood, and much of his will, with respect to moral good and evil, be known, against both which they have rebelled, and having sinned, will perish without law: though it may also include all such persons, who having been favoured with an external revelation, have professed to know God, and yet in works have denied him:
and that obey not the Gospel of the Lord Jesus Christ; of which Christ is the author, was the preacher, and is the sum and substance; which is good news and glad tidings of the grace of, God, of peace, pardon, righteousness, life, and salvation by Christ; which may be said to be obeyed, when it is received and embraced by faith, with and from the heart, and confession is made of it with the mouth, and the ordinances of it are submitted to; and which is called the obedience of faith, because faith without obedience is not right, and obedience without faith is of no avail: but all that hear the Gospel do not obey it; there are some that disbelieve and reject the doctrines and ordinances of it, and others that, do profess it, and do not yield a cordial and cheerful obedience to it; both may be reckoned among the disobeyers of it: and though the unbelieving Jews may be chiefly designed here, yet deists of every age and place, where the Gospel revelation has come, and carnal professors, and profane despisers everywhere, may be included; whose condemnation will be aggravated by the external light which has shone around them, and they have hated; the severest punishment will be inflicted on them; it will be more tolerable for Tyre and Sidon, Sodom and Gomorrah, than for such persons; see 1-Peter 4:17.
(z) Zohar in Genesis. fol. 63. 2.

In flaming fire--Greek, "In flame of fire"; or, as other oldest manuscripts read, "in fire of flame." This flame of fire accompanied His manifestation in the bush (Exodus 3:2); also His giving of the law at Sinai (Exodus 19:18). Also it shall accompany His revelation at His advent (Daniel 7:9-10), symbolizing His own bright glory and His consuming vengeance against His foes (Hebrews 10:27; Hebrews 12:29; 2-Peter 3:7, 2-Peter 3:10).
taking--literally, "giving" them, as their portion, "vengeance."
know not God--the Gentiles primarily (Psalm 79:6; Galatians 4:8; 1-Thessalonians 4:5); not of course those involuntarily not knowing God, but those wilfully not knowing Him, as Pharaoh, who might have known God if he would, but who boasted "I know not the Lord" (Exodus 5:2); and as the heathen persecutors who might have known God by the preaching of those whom they persecuted. Secondarily, all who "profess to know God but in works deny Him" (Titus 1:16).
obey not the gospel--primarily the unbelieving Jews (Romans 10:3, Romans 10:16); secondarily, all who obey not the truth (Romans 2:8).
Christ--omitted by some of the oldest manuscripts, and retained by others.

Taking vengeance - Does God barely permit this, or (as "the Lord" once "rained brimstone and fire from the Lord out of heaven," Genesis 19:24) does a fiery stream go forth from him for ever? Who know not God - (The root of all wickedness and misery) who remain in heathen ignorance. And who obey not - This refers chiefly to the Jews, who had heard the gospel.