Members of the Bcl-2 family are crucial integrators of survival and death signals in higher eukaryotes. Although recent studies have provided novel and quite unexpected insights into the mechanisms by which these proteins might issue life permits or death sentences in cells, we are still on the way to fully understand their modes of action. This review provides a snapshot on where we are on this journey and how we may exploit our knowledge on this family of proteins to unveil the mysteries of immune regulation.