Antidotes raised intricate questions concerning the relationship between elements and substances, shedding light on two opposing strategies for explaining the causal properties of complex composites. Reductionism holds that the powers of a material composite are identical to the sum of its individual constituents, meaning that the properties of medicaments can be explained solely by the qualities and interactions of their elemental components. In this view, composites act “by their whole substance” only insofar as their actions result from the modified contributions of their elements through mixture, a concept often framed in terms of “temperament” or “complexion.” By contrast, emergentism posits that composites generate novel causal properties irreducible to their elemental constituents. This chapter explores how this debate played out in the writings of Thomas Erastus and Girolamo Mercuriale, two prominent sixteenth-century physicians.