Montaigne’s skepticism was extremely influential in the early 17th century. His followers in France—Pierre Charron, J.-P. Camus, and La Mothe Le Vayer, among others—further popularized his views. Various French Counter-Reformers used the arguments of Montaigne and Sextus to undermine Calvinism. Montaigne’s skepticism opposed all sorts of disciplines, including the new science, and was coupled with a fideism which, in Montaigne’s case, many suspected to be insincere.

In the 1620s efforts to refute or mitigate this new skepticism appeared. A Christian Epicurean, Pierre Gassendi, himself originally a skeptic, and Marin Mersenne, one of the most influential figures in the intellectual revolution of the times, while retaining epistemological doubts about knowledge of reality, nevertheless recognized that science provided useful and important information about the world. The constructive skepticisms of Gassendi and Mersenne, and later of members of the Royal Society of England such as Bishop John Wilkins and Joseph Glanvill, developed the attitude of Sanches into a hypothetical, empirical interpretation of the new science.

René Descartes offered a fundamental refutation of the new skepticism, contending that, by applying the skeptical method of doubting all beliefs that could possibly be false (owing to illusion or deception by an evil demon), one would discover a truth that is genuinely indubitable—namely, “I think, therefore I am” (cogito ergo sum), and that from this truth one could discover the criterion of true knowledge—namely, that whatever is clearly and distinctly conceived is true. Using this criterion, one could then establish a number of truths: that God exists, that he is not a deceiver, that he guarantees the veracity of clear and distinct ideas, and that an external world exists that can be known through mathematical physics. Thus Descartes, starting from skepticism, claimed to have found a new basis for certitude and for knowledge of reality. Throughout the 17th century, skeptical critics—Mersenne, Gassendi, the reviver of Academic philosophy Simon Foucher, and Pierre-Daniel Huet, one of the most learned men of the age—sought to show that Descartes had not succeeded, and that, if he sincerely followed his skeptical method, his new system could only lead to complete skepticism. They challenged whether the cogito proved anything and whether it was indubitable; whether Descartes’s method could be successfully applied and whether it was certain; and whether any of the knowledge claims of Cartesianism were really true. Nicolas Malebranche, the developer of occasionalism (the view that all interaction between mind and body is mediated by God), revised the Cartesian system to meet skeptical attacks only to find his efforts challenged by the new skeptical criticisms of Foucher and by the contention of Antoine Arnauld that Malebranchism led to a most dangerous Pyrrhonism.

Various English philosophers, culminating in the 17th century in John Locke, tried to blunt the force of skepticism by appealing to common sense and to the “reasonable” person’s inability to doubt everything. They admitted that there might not be sufficient evidence to support knowledge claims extending beyond immediate experience. But this did not actually require that everything be doubted; by using standards of common sense, an adequate basis for many beliefs could be found. In France, Blaise Pascal, who presented the case for skepticism most forcefully in his Pensées (published posthumously in 1670), nevertheless denied that there could be a complete skepticism, because nature prevents it. Lacking rational answers to complete skepticism, humans must turn to God for help in overcoming doubt.

The culmination of 17th-century skepticism appears in the writings of Pierre Bayle, especially in his monumental Dictionnaire historique et critique (1697–1702). Bayle, a superb dialectician, challenged philosophical, scientific, and theological theories, both ancient and modern, showing that they all led to perplexities, paradoxes, and contradictions. He argued that the theories of Descartes, Malebranche, Benedict de Spinoza, and Gottfried Wilhelm Leibniz, when skeptically analyzed, cast in doubt all beliefs about the world, even the belief that the world exists. Bayle skillfully employed skeptical arguments about such things as sense information, human judgments, logical explanations, and the criteria of knowledge in order to undermine confidence in human intellectual activity in all areas. He suggested that humans should abandon rational activity and turn blindly to faith and revelation; they can therefore only follow their conscience without any criterion for determining true faith. Bayle showed that the various conceptions of religious knowledge were so implausible that even the most heretical views, such as Manichaeism (known for its cosmic dualism of good and evil) and atheism, made more sense. As a result, Bayle’s work became “the arsenal of the Enlightenment” in the 18th century, and he was regarded as a major enemy of religion. Although Bayle indicated in later works that he did hold some positive views, he presented no answers to his skepticism. There is still much scholarly debate as to what his actual position was.