Chronic depolarization greatly increases the survival of many types of neurons in culture. In at least some cases this enhancement of survival consists of the suppression of programmed cell death, a type of death occurring in developing neurons deprived of sufficient neurotrophic factor support. Available evidence suggests that the effect of depolarization on survival is mediated by a sustained rise of cytoplasmic free Ca2+, apparently caused by influx of Ca2+ through voltage-gated channels. This review discusses what is known about the mechanism by which prolonged depolarization and increased intracellular Ca2+ promote survival.