Placebos have been used since about 1950 in evaluation and interpretation of drug efficacy, especially of new drugs, and in comparison with existing compounds to establish their clinical therapeutic value. There are a number of problems connected with use of an "inert nothing" the informed consent, which is required in a human experiment, the doctor's consciousness of deceitful behaviour, the potential risk for the patient and the doctor, the high effect rate of placebos (+/- 35%), unexpected side-effects, dependency of patients on placebos, discovery by the patient of the placebo treatment, factors independent of the medication, such as the doctor's bias, the nurses influence, the significance of colour, the inconsistency of placebo-reactor or non-reactor types and the genetic state of the patient, as well as the problems associated with a double blind test, which can hardly be used when a patient has previously received a medicine, such as morphine, with its euphoric effect, and the colour change produced in urine by drugs like rifampicin or riboflavin. Only a well-trained and experienced clinical observer should employ a placebo in establishing the therapeutic value of drugs whilst avoiding undesirable pitfalls.