Antidepressants play the major role in treating depressive patients not only due to the fact that they have to undergo the most rigorous proof of efficacy but also because they are easy to apply in the everyday clinical practice. Nearly all psychiatrists and general practitioners treating depressive patients agree about the relevance of antidepressants in the treatment of depressive patients. However, a number of meta-analytic studies recently challenged this belief and it has been put up for discussion to psychiatry/clinical psychopharmacology whether the efficacy of antidepressants is clinically relevant. Despite that all medication were judged to have sufficient data to receive approval from the FDA and the EMA and other agencies worldwide, some authors went further and questioned the effectiveness of antidepressants. They even proposed that "alternative" therapies of unproven efficacy or of proven negative efficacy should be preferred to medication. These authors do not take into consideration that for methodological reasons it is not acceptable to deduce too extensive conclusions. Some assumptions they rely on, like the suggestion of NICE, which regards a mean placebo-verum difference of 3 HAM-D points as clinically relevant, is downright arbitrary on statistical grounds, and not supported by empirical findings or by expert opinion. It seems that the difference in change in HAM-D score between the active drug and placebo is somewhere between 2 and 3, with maybe some agents performing a little better than others. It is uncertain whether initial severity determines response; different interpretations exist. However, much more important for the evaluation of the clinical relevance is the result of the responder/remitter analysis, which compares the relative frequency of these categories between the placebo and verum groups. This approach results in a number needed to treat (NNT) of 5-7. In evidence-based medicine such a NNT is traditionally regarded as a sign of moderate to strong efficacy and corresponds to the referring values of many therapies, which e.g. are standard therapies in internal medicine. However, from many meta-analyses it is clear that when concepts of evidence-based medicine and health economy are applied, which are far away from clinical thinking, problems occur and results are very difficult to interpret in clinical terms.