Neurochemical theories ascribe the therapeutic action of antidepressant drugs to their influence on neurotransmission level processes. However, the empirical and conceptual gap between neurochemical processes and depressive symptoms and signs limits the explanatory power of these theories. Research into the effects of antidepressant drugs on human sleep could possibly help to bridge this gap. A review of the literature shows that almost all antidepressant drugs suppress REM sleep. Within the area of research into the relation between sleep and depression, several theories have been developed offering explanations of the sleep characteristics of depressives and the therapeutic effect of sleep deprivation. In this paper the contribution of these theories to a better insight into the therapeutic mechanism of antidepressant drugs is evaluated. The authors conclude that especially the cholinergic-aminergic balance theorye and the two-process theory stimulate the development of interesting research hypotheses.