Neuronal death may be mediated by common upstream mechanisms that differ mechanistically in the rate (days versus hours) and severity of cellular stress. Cellular stress can destroy neurons through pathways causing apoptosis and necrosis. It will be important to evaluate the specific mechanisms of neuronal necrosis in vivo to compare with the mechanisms of neuronal apoptosis in vivo. These comparisons will provide valuable information on the signaling pathways that dictate neuronal cell death. We believe that such comparisons will also aid in validating and understanding the concept of the cell death continuum. Understanding the cellular and molecular mechanisms of neuronal cell death can lead to new therapeutic approaches critical for the future prevention of neurodegeneration in chronic and acute neurological disorders and can expand the field of cell death biology.