During the last decade a number of meta-analytic studies have been published and they triggered a debate on the true clinical usefulness of antidepressants. The current article comments on problems within the randomized controlled trials design, the study samples, the psychometric scales, the methods of meta-analysis, the interpretation of the results, and the reporting of conflicts of interest. Although the meta-analyses published so far agree that medication works in severe depression, they question its efficacy in mild cases. However, several methodological issues should be clarified before conclusions are definite. Different methods give different results and similar results seem to entertain a variety of interpretations. In the future it is important to address all of these problems, and to improve methodology on the basis of clinically informed choices. Otherwise, meta-analysis risks alienation from clinical reality and thus risks becoming the 21(st) century psychoanalysis.