The main theme in this essay is faith and how faith interacts with knowledge. Montaigne sets out to defend the fifteenth century theologian Raymond Sebold against claims of atheism. These had been leveled against Sebold by the church because he was perceived to be suggesting humans should seek rational support for their faith—that is, that they should seek knowledge and therefore prove that their faith is justified. The argument Montaigne makes is that Sebold has been misinterpreted: what he was really saying was that seeking knowledge helps us understand God better. Through the knowledge we derive from our human senses, we can actually deepen our faith and become better acquainted with God; however, at the same time, there can be no knowledge without God.

Montaigne returns again and again to this question of knowledge, what knowledge really is, whether it is evil, and whether it is actually possible for humans to know anything. He touches upon several different attitudes to theological knowledge, including dogmatism, pyrrhonism (in which we simply refrain from all judgement) and academic skepticism. Ultimately, however, he seems to be suggesting that any kind of dogmatic belief is vanity because humans cannot really know anything.

Montaigne examines this point from various angles. He suggests that we are not more important than animals, who know nothing, because anything we know, we can only know because of God. In this sense, the theme of knowledge interacts with the theme of truth and what is true. According to Montaigne, it is impossible to know anything when we have no actual understanding of the real truth of things—only God knows this. As such, any knowledge that humans have is only possible because of God's grace, and it is hubris to believe that one knows anything more than anyone else. The only being who really is capable of true knowledge is God, because only God knows the truth.