Among psychiatric disorders, depression and generalized anxiety are probably the most common stress-related illnesses. These diseases are underlain, at least partly, by dysfunctions of neurotransmitters and neurohormones, especially within the serotoninergic (5-HT) system and the hypothalamo-pituitary-adrenal (HPA) axis, which are also the targets of drugs used for their treatment. This review focuses on the nature of the interactions between central 5-HT and corticotrope systems in animal models, in particular those allowing the assessment of serotoninergic function following experimental manipulation of the HPA axis. The review provides an overview of the HPA axis and the 5-HT system organization, focusing on the 5-HT(1A) receptors, which play a pivotal role in the 5-HT system regulation and its response to stress. Both molecular and functional aspects of 5-HT/HPA interactions are then analyzed in the frame of psychoaffective disorders. The review finally examines the hippocampal neurogenesis response to experimental paradigms of stress and antidepressant treatment, in which neurotrophic factors are considered to play key roles according to the current views on the pathophysiology of depressive disorders.