Curt Daniel calls this "Knox's major theological work."
Moreover, he states that this is "more than a short answer (to the Anabaptist--RB, 468 pages), it is a complete exposition and defence of the Reformed doctrine at the height of the Scottish Reformation" which helped "guide early Presbyterianism and build the theological bridge between Edinburgh and Geneva."
Furthrermore, Walker writes: "Very far from being a mere iconoclast, he (Knox) was also a great teacher of his country men... the long and elaborate treatise on Predestination, in which the doctrines of grace and of divine sovereignty are so vigorously, yet upon the whole so wisely, asserted and maintained -- gives Knox a high place among theologians" (Theology and Theologians of Scotland).
This work was much esteemed by Knox's Puritan friends in England and "Calderwood, in summing up Knox's character, remarks: 'How profound he was in divinity, that work of his upon Predestination may give evidence" (Laing. ed., p. 17).
Furthermore, Laing beautifully sets the context of this work, writing,
"At the Period of the Reformation, there prevailed among Christians of all denominations the general belief, 'that the salvation of man depends on the free grace of God. But they differed on the question, whether the divine decree which has reference to this point is unconditional, or depends on the conduct of man, whether it is general or particular...
Thus it happened, that Roman Catholics, Arminians, and most of all Socinians endeavoured, in the sense of Pelagianism, or Semi-pelagianism, to reconcile the divine decrees with human liberty. On the other hand, both Lutherans and Calvinists, following the example of Augustine, rejected the notion of the freedom of the will, and denied every co-operation on the part of man.
Nevertheless it is a striking fact, that the Lutherans avoided the strict consequences of the Augustinian system, and asserted that the decrees of God are conditional, while the Calvinists not only admitted the necessity of those consequences, but having once determined the idea of Predestination, went so far as to maintain that the fall of man itself was predestinated by God, (Supralapsarianism)."
Quoting freely from Calvin, his major influence in this work, Knox lays low the heresy that man plays any part in his own salvation. This heresy, of man's pretended ability to save himself (in any way), is at the root of all defection from the sovereign God of Scripture and is rampant today!
As Kevin Reed notes, in refuting this Anabaptist, Knox unequivocally states, "For with the Pelagians and papists, you have become teachers of free will, and defenders of your own justice," clearly recognizing that, "the defence of man's free will, to do good and avoid evil," is "the damned heresy of Pelagius."
Moreover, regarding this work, Reed continues, "A perceptive reading of this dispute will reveal the parallels between the Anabaptists and modern proponents of free will. Advocates for free will are commonly found among Baptists, 'evangelicals,' Charismatics, and cultists. Their line of argumentation is virtually identical to that of Knox's opponent" (Kevin Reed, John Knox the Forgotten Reformer, pp. 219-20).
This book contains significant information for defeating the forces of antichrist today; for he (especially ecclesiastical antichrist) continues to manifest the same spirit of error seen in the days of Knox -- deceiving men into thinking that they, in some way (be it ever so small), are able to save themselves.