Injury to the brain usually manifests not in a diffuse uniform manner but rather with selective sites of damage indicative of differential vulnerability. This question of neuronal susceptibility has been one of major interest both in disease processes as well as damage induced by environmental factors. For experimental examination, brain structures with obvious neuronal subpopulations and organization such as the cerebellum and the hippocampus have offered the most promise. In the hippocampus distinct neuronal populations exist that demonstrate differential vulnerability to various forms of insult including ischemia, excitotoxicity, and environmental factors. The more recent data regarding the presence of neuronal progenitor cells in the subgranular zone of the dentate offers the opportunity to expand such experimental examination to the process of injury-induced neurogenesis. Thus, more recent studies have expanded the examination of the hippocampus to include models of damage to the dentate neurons in addition to the highly vulnerable pyramidal neurons. A number of these models are presented for both human disease and experimental animal conditions. Examination of the responses between these distinct cell populations offers the potential for understanding factors that are critical in neuronal death and survival.