Like Descartes, Comenius also had his own peculiar “crusade” against skepticism. Comenius reflects on skepticism from four perspectives: an existential dimension, linked to “selfhood” and the subject’s isolation; a methodological-reformist perspective, which interprets skepticism as a consequence of the disorder of knowledge and the absence of an adequate method; a theological approach inspired by the Pauline tradition; and, finally, an ethical-intellectualist dimension that understands truth as an indispensable condition for the reform of human affairs. These four perspectives are attempts to discredit skepticism as a way of life incompatible with Comenius’s pansophic project.