A growing family of genes that share homology with the bcl-2 proto-oncogene is involved in the regulation of cell death. Many of these proteins show widespread expression and are expressed in the nervous system in developing and adult organisms. A physiologic role for Bcl-2 and Bcl-x in neuron survival has been shown. In addition, these proteins have been shown to protect neurons from a wide array of toxic insults. In this review, we discuss the Bcl-2 family of proteins with regard to their structure and interactions. We then discuss the role of apoptotic cell death in the development of the nervous system and as a response to neuronal injury. Lastly, we discuss the evidence for a role for these cell death regulators in neuronal death decisions.