Recent studies have strengthened the role of the abnormalities in neurotrophic pathways in the pathophysiology of depression. It has been shown that the depletion of growth factors, particularly brain-derived neurotrophic factor, may result in depression-like behavior in animals and may induce cellular changes that are reminiscent of those observed in depressed patients. Some authors even suggested that increased neuronal cell loss may contribute to the pathogenesis of depression. Hence, appreciable interest has been focused on the trophic and antiapoptotic effects of antidepressant drugs. In this paper, we put emphasis on the contribution of hippocampal atrophy, increased cell death and alterations in trophic factors to the pathogenesis of depression and their relationship to the potential of antidepressants to reverse these changes by modulating trophic factor cascades and preventing apoptosis. First, evidences for increased hippocampal atrophy and cell death in depression are discussed, followed by a review of selected studies of special interest that concern antiapoptotic action of antidepressant drugs. Next, depression-related neurotrophic abnormalities and their reversal by antidepressants are depicted. Finally, relationships among neurotrophins, antiapoptotic proteins and antioxidant enzymes in the pathology and treatment of depression are pointed out.