This review of the literature concerning the biochemical factors of resistance to antidepressants is essentially based on the anomalies of neurotransmitters and the enzymes which regulate them. In the case of 5HIAA, because of the bimodal distribution in depressed patients, it appears to be generally accepted that when a low level of this catabolite is found in the cerebrospinal fluid, this may represent a factor of resistance to noradrenergic antidepressants, or even to all antidepressants. In contrast, a high level of this catabolite represents a factor of poor response to serotoninergic antidepressants. Low levels of urinary MHPG predict a poor response to serotoninergic antidepressants, while high levels are observed in cases of depression resistant to noradrenergic antidepressants. MAO activity, evaluated after two weeks' treatment with MAOI, is considered to be a biochemical factor of resistance when it is inhibited by less than 80%. High levels of COMT (related to the degree of anxiety and agitation) reflect a poor response to noradrenergic antidepressants. Finally, a number of strategies designed to control resistant depression (reserpine, lithium carbonate, ...) could, in certain cases, suggest the existence of a functional defect in the serotoninergic systems.