Demonstration of neurogenesis in adult brain represents a major advance in our understanding of the cellular mechanisms underlying neuronal remodeling and complex behavior. Recent studies from our laboratory and others demonstrate that chronic administration of an antidepressant, including either a 5-HT or norepinephrine selective reuptake inhibitor, up-regulates neurogenesis in adult rodent hippocampus. Up-regulation of neurogenesis could block or reverse the effects of stress on hippocampal neurons, which include down-regulation of neurogenesis, as well as atrophy. The possibility that the cAMP signal transduction cascade contributes to the regulation of neurogenesis by antidepressants is supported by previous studies and by recent work. Although additional studies must be conducted to determine the significance of adult neurogenesis in humans, these findings will stimulate new avenues of research to identify the cellular and molecular basis of stress-related mood disorders as well as the development of novel therapeutic strategies.