Émile Meyerson (1859-1933) helped inaugurate a philosophical tradition in early twentieth-century France – épistémologie – which harkened back to Auguste Comte's historical method, analyzing science in order to grasp the nature of human reason, while rejecting orthodox positivism. Meyerson's own épistémologie had ambitious, specifically Kantian, aims: to reveal principles universally necessary for scientific knowledge, thereby providing "prolegomena to all future metaphysics." This historicized Kantianism was the centerpiece of a vibrant intellectual circle – the "Meyerson Circle" – which included such luminaries as Alexandre Koyré, Hélène Metzger, Léon Brunschvicg, Lucien Lévy-Bruhl, and Gaston Bachelard. While some of these thinkers are now garnering interest among Anglo-American philosophers – especially in light of "historical epistemology" (see Ian Hacking, Lorrain Daston, and Arnold Davidson) and revitalized post-Kuhnian concerns about the rationality of science (see Michael Friedman) – Meyerson's own contributions remain underappreciated. Despite his role as intellectual godfather and praise from such readers as Albert Einstein, Louis de Broglie, Ernst Cassirer, Walter Benjamin, Arthur Lovejoy, Karl Popper, W. V. O. Quine, and Thomas Kuhn, no books and only a few articles have been published on Meyerson in English since 1966. This is unfortunate especially given his relevance for contemporary interest in neo-Kantian approaches to the history and philosophy of science. This dissertation contextualizes Meyerson's épistémologie historically – focusing on both the preceding French traditions of positivism, spiritualism, neo-Kantianism, and conventionalism and how Meyerson's views anticipate such thinkers as Quine and Kuhn – and assesses its viability as a philosophical project today. My aim is to revitalize a broadly neo-Kantian approach to epistemology, which bears in fruitful ways on contemporary problems in philosophy of science – and philosophy more broadly – while remaining distinct from other neo-Kantianisms defended today. Specifically, I argue that Meyerson is unique for accepting epistemological holism along with a Kantian commitment to the essential "oneness" of human reason; and defending a distinctive brand of scientific realism along with a Kantian commitment to the essential unknowability of nature in itself. I conclude by showing how Meyerson's épistémologie provides a powerful framework for practicing a historically-grounded form of philosophy today.