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This volume presents twelve original essays, by an international team of scholars, on the relation of John Locke's thought to Descartes and to Cartesian philosophers such as Malebranche, Clauberg, and the Port-Royal authors. The essays, preceded by a substantial introduction, cover a large variety of topics from natural philosophy to religion, philosophy of mind and body, metaphysics and epistemology. The volume shows that in Locke's complex relationship to Descartes and Cartesianism, stark opposition and subtle 'family resemblances' are tightly intertwined. Since the turn of the twentieth century, the theory of knowledge has been the main comparative focus. According to an influential historiographical conception, Descartes and Locke form together the spearhead in the 'epistemological turn' of early modern philosophy. In bringing together the contributions to this volume, the editors advocate for a shift of emphasis. A full comparison of Locke's and Descartes's positions should cover not only their theories of knowledge, but also their views on natural philosophy, metaphysics, and religion. Their conflicting claims on issues such as cosmic organization, the qualities and nature of bodies, the substance of the soul, and God's government of the world, are of interest not only in their own right, to take the full measure of Locke's complex relation to Descartes, but also as they allow a better understanding of the continuing epistemological debate between the philosophical heirs of these thinkers.