Increasing evidence implicates aberrant apoptosis as a fundamental cause of neurodegenerative diseases. Thus elucidating the underlying causes of neuronal programmed cell death may foster the development of therapeutic interventions. Research in the last 15 years provided a solid foundation for understanding molecular mechanisms of neuronal apoptosis. This review discusses the major molecules and signaling pathways leading to neuronal survival or apoptosis with emphasis on several small molecule inhibitors that target neuronal survival with the hope of impeding the detrimental effects of neurodegenerative diseases.