Although initially disregarded compared to prion pathogenesis, the functions exerted by the cellular prion protein PrPC have gained much interest over the past two decades. Research aiming at unraveling PrPC functions started to intensify when it became appreciated that it would give clues as to how it is subverted in the context of prion infection and, more recently, in the context of Alzheimer's disease. It must now be admitted that PrPC is implicated in an incredible variety of biological processes, including neuronal homeostasis, stem cell fate, protection against stress, or cell adhesion. It appears that these diverse roles can all be fulfilled through the involvement of PrPC in cell signaling events. Our aim here is to provide an overview of our current understanding of PrPC functions from the animal to the molecular scale and to highlight some of the remaining gaps that should be addressed in future research.