Monoaminergic systems, and in particular serotoninergic neurons of the raphe system, have been involved in the physiopathology and treatment of major depression in a great number of studies. One of the most reproducible effects of antidepressant treatment is the increase of central 5-HT (serotonin) tone. However, the identification of novel potential therapeutic targets (neurohormones, neuropeptides) for treating depression has led to elaborating novel cellular and molecular concepts accounting for stress-related mood disorders. In particular, recent studies have demonstrated that chronic administration of all classes of antidepressants up-regulates neurogenesis in adult rodent hippocampus. The possibility that structural remodelling may contribute to the physiopathology of mood disorders provides new avenues of research toward understanding the cellular basis of mood disorders.