Apology for Raymond Sebond is the longest and most famous essay in Essays. Although it begins as a defense of the theologian Raymond Sebond, it becomes a wide-ranging meditation on human knowledge, faith, and humility.

Its core ideas include:

The essay's famous underlying question is "What do I know?" ("Que sais-je?"), which became Montaigne's personal motto. Rather than leading to despair, this skepticism encourages modesty, curiosity, and a recognition that certainty is rare.

Today, the essay is regarded as one of the foundational works of modern philosophical skepticism and had a profound influence on later thinkers such as Blaise Pascal, René Descartes, and David Hume.