This essay provides a thorough reading of Gilles Deleuze’s (1925–95) philosophy of nature and the way music relates to this philosophy. It does so with regards to changes in the view of nature in 20th century science, especially in the theories of self-organisation as developed by, among others, Ilya Prigogine. Deleuze’s metaphysics is viewed in relation to these theories, and is also compared to the philosophy of Immanuel Kant, which is related to classical science. The essay then investigates certain key issues in Deleuze’s philosophy concerning difference and univocity (or immanence), developed in his doctoral thesis Différence et répétition (1968). Also, certain aspects of the further evolution of this philosophy of immanence in Mille plateaux (1980), co-written with Félix Guattari, are examined. The essay then studies the role of aesthetics in Deleuze’s philosophy, and the way he transforms the aesthetics of Kant. The following chapter deals with Deleuze & Guattari’s primary text concerning music, ”De la ritournelle” in Mille plateaux. In this text, they develop a highly abstract concept of music, which, in their philosophy, is: 1) granted a cosmological reach regarding rhythms and motives; 2) made an essential aspect of the emergence of art, which they find in animals creating a territory (especially in the songbird); 3) used to discuss Baroque/Classicist, Romantic and 20th century musical styles. Apart from analysing these aspects, this chapter focuses on 20th century music, with a thorough examination of Gustav Mahler and of spectral music, demonstrating that Deleuze’s philosophy can deepen the understanding of this music. The chapter also discusses problematic tendencies in Deleuzian research on contemporary music, which does not take the entirety of Deleuze’s philosophy of nature into account. This essay argues that such knowledge is necessary to correctly examine the implications of Deleuze & Guattari’s philosophy of music. The lack of awareness of Deleuze’s philosophy of nature is also significant in the critique that Deleuze’s aesthetics has received by Jacques Rancière, which is analysed in the final chapter. This chapter also discusses Michael Gallope’s reading of Deleuze & Guattari, in which he makes a distinction between a metaphysical and an ethical-aesthetic philosophy of music. Although the relation between metaphysics, ethics, and aesthetics, is key to understanding their philosophy of music, this essay argues that Gallope’s idea of what sort of music they advocate is incorrect.