Craver’s (2007) account of explanation in neurobiology offers one of the most sophisticated explications of the mechanism concept. This paper argues that despite groundbreaking advances in understanding mechanistic explanation, serious challenges remain. The first goal of this paper is to address the notorious problem of explanatory relevance concerning mechanistic explanation. I argue that Craver underestimates the importance of pragmatic constraints on the individuation of mechanisms, and that his suggestion for a solution of the explanatory relevance problem is therefore insufficient on several counts. My second goal is to develop an alternative that explicitly incorporates both pragmatic and ontic aspects of mechanism individuation.