The central issue raised in this paper is: can stress cause depression? Phrased more precisely: can stress cause brain disturbances thought to underlie (certain forms of) depression or particular components of the depressive syndrome. Focussing on 5-HT and the stress hormones, this question was answered in the affirmative, based on the following two considerations: (1) changes in the 5-HT and stress hormone systems produced by sustained stress, mimic to a substantial extent the disturbances in these systems that may be observed in depression; (2) substantial evidence indicates that the 5-HT and stress hormone disturbances in depression are of pathophysiological significance and not merely a consequence of the depressed state or a product of stress generated by the depressed state. Furthermore, the question was raised whether a depression type could be identified particularly stress-inducible. This question, too, was answered in the affirmative. The depression type in question was named anxiety/aggression-driven depression and characterized on three levels: psychopathologically, biologically and psychologically. Preferential treatment of this depression type was discussed. In studying stress-inducible depression biological depression research should shift focus from depression per se to the neurobiological sequelae of stress. Treatment of stress-inducible depressions and particularly its prevention should be geared towards reduction of stress and stress sensitiveness, utilising both biological and psychological means.