From the later Middle Ages throughout the early modern period, the biblical injunction to “test the spirits” became the subject of an increasing number of treatises and practical case studies. The phrase was understood as an imperative to verify whether the preternatural abilities claimed by some individuals—chiefly women—derived from a divine, or rather from a demonic, spiritual origin. Efforts to locate spirits within the body, to map their interactions with individuals, and to exorcize them if they were determined to be evil in character, all were implicated in this centuries-long effort to distinguish good from evil inspiration. While it is self-evident that such practices had religious implications, this article argues that they also had much broader ramifications for the intellectual history of European culture. As the discernment of spirits grew and flourished, it helped foster the development of a culture of testing unseen dimensions of reality more broadly. The discourse of discernment of spirits represents a form of epistemological inquiry—a concern with verification of assumed truths, and with testing evidence—that challenges conventional narratives about the rise of experimental science.