Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches should operate in close interaction, each providing additional information to the other approach. However, in practice the animal model approach seems to be rather independent from the human studies. In a critical evaluation of the available animal models of depression, Willner concluded that none of the models fulfilled the criteria of a sufficient face, construct and predictive validity. Although this evaluation was made ten years ago, we feel that the situation has improved very little since that time. Most animal models fail to sufficiently mimic both the etiology and the symptomatology of human depressive disorders. With respect to the etiology, stress and major life events are generally considered to be an important factor in the development of depression. Most of the animal models however use stressors which bear little or no relationship to the biology of the species, i.e. to the situations an animal may meet in its everyday life in a natural habitat. Moreover, these models do not pay attention to the temporal dynamics of the disease. In humans, the disease is characterized by its gradual onset, which is often preceded by symptoms of anxiety. Moreover, a relatively large number of patients suffers from recurrent episodes of depression, which tend to occur with decreasing intervals and increasing duration and severity. If we want to improve our knowledge of the causal mechanisms of depression, animal models which allow an experimental analysis of the temporal dynamics of the disease are essential.