John Locke famously claimed that our idea of substance is but a confused idea of “something we know not what.” However, he also thought that the idea of substance is a fundamental part of our ideas of ourselves and the objects surrounding us—of objects we do know. Interpreting this apparently ambivalent stance has long been a major challenge for Locke scholarship. In this article, I argue that the leading interpretations of Locke's conception of substance have failed to resolve this tension because they have misconstrued the source of Locke's skepticism about our knowledge of what substance is. This skepticism, I argue, issues from an observation about the signification of the term “substance”: Locke maintained that the philosophical usage of the term is irremediably equivocal. This reading allows us to acknowledge that Locke could consistently hold that ordinary objects, such as persons, horses, or trees, are paradigmatic examples of substances. It also points to a better appreciation of how Locke's discussion of substance relates to the scholastic conceptions of substance he tried to overcome.