Developmental cell death is an integral part of the many adaptive strategies employed during ontogeny for generating the mature nervous system. There is increasing evidence that some of the mechanisms that regulate the death and survival of developing neurons and that of mature neurons following injury or in neurologic disease are similar. This chapter discusses several hypotheses of the etiology of amyotrophic lateral sclerosis (ALS). Neuronal cell death observed in brains of Huntington's disease (HD) patients, mutant Htt-expressing transgenic mice or neurotoxin-treated rats occurs through apoptosis. Recent studies reveal continuity in the molecular mechanisms by which apoptosis occurs in the various animal models of Parkinson's disease (PD). The chapter describes the cellular and molecular events of spinal cord injury (SCI) and suggests potential strategies for therapeutic rescue. Anti-apoptotic agents, including neurotrophic factors (NTFs), are necessary but not exclusive components of any effective therapy for neurodegenerative disease and neuronal injury.