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The theme of the “clinical” runs through Gilles Deleuze’s work without appearing explicitly as a major concept. However, the borrowing of this term from the medical field implies a critical discussion on the ways in which medicine, including psychoanalysis, analyzes symptoms and determines clinical presentations. The challenge for Deleuze is to emancipate the clinical approach from its medical objective of identifying a patient’s condition with a pathology, by proposing to make clinical practice the means of describing the signs emitted by a subject experiencing new physical and mental states. This broadening of the meaning of clinical practice makes it a method of philosophical investigation whose objective is to follow signs usually judged aberrant or even “asignifiant,” forcing the gaze and the discourse to invent ways of seeing and saying. In this article, we first seek to define the Deleuzian meaning of the clinical approach, and then we show how this method is part of the project of a philosophy of difference. Finally, using examples, we clarify the central role of art (in particular literature) in a “clinical approach to difference.”