This paper traces the analogy between the making of bread with ferment (leaven or yeast) and theories of metallic transmutation throughout the Middle Ages. For this purpose it surveys several medieval alchemical writings, including Hortulanus’s influential Commentary on the Emerald Tablet. In this work, the ferment, an essential ingredient of the philosophers’ stone, is portrayed less as an active agent and more as the passive, nutritive earth (terra nutrix) which combines with the soul (anima) in order to yield the stone (lapis). I argue that the background of these theories has both a practical and a medical-theoretical dimension. The practical aspect derives from historical everyday practices of making bread from sourdough, and using old yeast “starter” as a kind of inoculum to speed up the fermentation of a new batch of fresh dough. The medical-theoretical framework for the understanding of ferment action was likely provided by the widely influential Galenic idea of whole substance action (Gr. καθ᾽ὅλην τὴν οὐσίαν, Lat. tota substantia), initially developed by Galen in pharmacology and later imported into alchemy via Arabic medicine. Together, these aspects converge into a successful model of “inoculation-emergence,” which underlies many medieval and early modern theories of fermentation, both medical and alchemical.