Placebo effects are well-known phenomena in medicine and biology. In fact, placebos are used as control conditions in randomized cross-over clinical trials to validate new treatments. Only recently, however, has it become apparent that the conditioning and/or expectation effects provided by the experience of placebos can influence the results of clinical trials. It seems that combining shams and sequences has prejudiced the conclusions provided by cross-over designs. Frighteningly, this bias is always in the same direction, namely to increase the risk of rejecting potentially valid treatments. New models for clinical trials should be encouraged if we wish to market new and truly valid treatments.