The placebo effect is a well-known phenomenon through medicine and has been used as a treatment in many different pathologies. Nowadays it is being used as a control for the design of trials about the new psychotropic drugs. Within Psychiatry and more specifically regarding the affective disorders, responses to the use of inactive substances have been more frequently described and the rates recorded go from 20% to 49%.We have made a review of the literature published in this field in order to identify the predictors which are possibly involved in those patients with depression who have positive or negative responses to placebo. The most significant data come from the social, nosological, clinical, evolutive and, above all, neuroendocrinologic predictors. To finish, it is important to remark how inconsistent and heterogeneous is the response to placebo, as well as the ethic and legal problems that its use can carry.