Placebos are medication surrogates that are able to improve symptoms in patients when prescribed by a doctor and for a patient, and that cannot be explained by a drug. In clinical testing and presumably also in clinical routine, placebo effects contribute substantially to the efficacy of medicines, at least with every-day diseases and complaints. Placebos on the one hand, and the mechanisms the response on the other, have not interfered with the development on novel drugs in past years, but have also brought about research that investigates its mechanisms and public interest in its clinical use in everyday medicine. Current knowledge grows by about 10.000 publications per year on placebo-controlled studies, and by nearly 100 papers on the placebo effect itself. This review will focus on the history of placebo use in medicine, on ethical issues related to the use of placebos, on methodological problems in placebo-controlled trials and their alternatives, and on mechanisms of the placebo response in clinical and experimental research, e.g. on type, size, dynamics, determinants, and predictors of the placebo response in the literature.