It is now generally accepted that the birth of new neurons occurs in brain areas such as hippocampus throughout the lifespan. The waning and waxing of neurogenesis in hippocampus is proposed as a key factor in the decent into and recovery from depression. If hippocampal neurogenesis was blocked, antidepressant would lose its behavioral effects in behavioral models of depression. Long-term, but not short-term, treatment with different classes of antidepressant could stimulate neurogenesis in the hippocampus remarkably. As the regulation of adult neurogenesis continues to be identified, it will provide novel avenues of studying the mechanism and developing pharmacological agents for depressive disorder.