Pestilential diseases formed a category of epidemic and often fatal diseases, whose outbreak, causes and treatment were challenging to explain in the Renaissance. In exploring this theme in sixteenth–century Galenic medicine, I examine the Platonic account of “occult” diseases and treatment that was proposed by the French physician Jean Fernel (1497–1558). While Fernel developed a philosophical explanation of pestilential diseases in On the Hidden Causes of Things (1548), he also suggested a therapeutic application in his Pathologia (1567), Therapeutices (1567) and posthumous Consilia (1582). By considering Fernel’s synthesis of ancient, medieval and Renaissance medical approaches to plague and pestilence, this chapter traces his views on astral causation, poisonous seeds and the innate heat in relation to pathology, pharmacology and therapy.