Here, the authors address the question whether the administration of placebo, in clinical trials of drugs to be registered or already registered, is ethically acceptable and/or scientifically useful. An important issue, particularly in view of the different opinions emerging in the international scientific community. Since many diseases are already treatable with established therapies and drugs, clinical trials should be performed mainly with placebo containing the appropriate active compound, in agreement with the Helsinki declaration. Active placebo should be employed when slightly modified compounds are tested and when trials are in phase 2/b, 3 or 4. The use of active placebo in these settings would be more correct from a scientific, ethical and economical point of view.