In this dissertation, I analyze the works of Nietzsche's Middle Period (as he called it, 'The Free Spirit Series') as an attempt to overcome the opposition between naturalism and Kantianism by criticizing each from the perspective of the other. By drawing on recent scholarship on Nietzsche's engagements with post-Kantian philosophy and on late nineteenth-century science and philosophy of science, I show how, as Nietzsche works through these shifts in theoretical perspective, he presents progressively more sophisticated attempts to work out the consequences of his conviction that autonomy must be naturalized and historicized. I conceptualize Nietzsche's project in terms of 'the collapse of transcendence': the rejection of all non-naturalistic sources of normativity. The collapse of transcendence is first broached in the criticisms of morality in Human, All-too-Human, and culminates in the announcement of 'the death of God' in The Gay Science. Nietzsche analyzes the collapse of transcendence in both psychological and historical terms. Psychologically, the collapse of transcendence is a withdrawal of affective investment in other-worldly sources of normativity. Historically, the collapse of transcendence is caused by a conflict between the results and method of modern natural science and traditional (i.e. foundationalist) self-understandings. On my account, Nietzsche shows how the collapse of transcendence is a condition of possibility for the emergence of 'free spirits' who are able to acknowledge and affirm the collapse of transcendence; they no longer desire unconditional, absolute normativity. In contrast to the Kantian question, 'What are the formal conditions of any possible autonomy?' Nietzsche asks, 'What are the material conditions of autonomy for us now?' Nietzsche must therefore develop an account of autonomy as self-fashioning consistent with the rejection of the desire for the absolute. In contrast to other interpretations, I argue that Nietzsche, at least in the Free Spirit series, should be interpreted as an Enlightenment modernist whose apparently radical claims are undergirded by a naturalistic critique of Kant's critical philosophy.