I argue that Émilie Du Châtelet breaks with Christian Wolff regarding the scope and epistemological content of the principle of sufficient reason, despite his influence on her basic ontology and their agreement that the principle of sufficient reason has foundational importance. These differences have decisive consequences for the ways in which Du Châtelet and Wolff conceive of science.Principles of sufficient reason dictate that everything in a certain domain has a reason or ground. Already among early modern rationalists, there was disagreement over how such principles are to be understood and what might follow from them. While their domain might encompass everything in general, many early modern thinkers preferred principles with a more restrictive scope. As the noncommittal reference to reasons or grounds in my formulation suggests, opinions also differed on what epistemological and metaphysical consequences could be drawn from principles of sufficient reason (Carraud 2002).Émilie Du Châtelet prominently discusses a Principle of Sufficient Reason (PSR) in her 1740 Institutions de Physique. The PSR plays a systematically important role in her account of understanding and of science, and also backs more specific philosophical commitments.Du Châtelet sometimes called the Institutions her Essay on Metaphysics, and its metaphysical commitments are plainly influenced by Christian Wolff, who took his own PSR to have decisive consequences for science. 2 The Institutions largely adopts his ontology of substances, accidents, and modes, as well as his idea that some fundamental substances, though not mind-like, are simple and non-spatiotemporal (1720, §900; 1725a, I.23; Stan 2018).