Clinicians have long known that context is important in any medical treatment and that the words and attitudes of doctors and nurses can have great impact on the patient. There is now experimental evidence indicating that the medical context influences specific neural systems. The importance of the context is shown by the lesser effectiveness of hidden administrations of analgesics compared with open ones. Because the placebo effect is a context effect, its study has been useful in clarifying this complex issue. There are now several lines of evidence that placebo analgesia is mediated by endogenous opioids and placebo motor improvement by endogenous dopamine. Moreover, a placebo treatment is capable of affecting many brain regions in depressed patients. All these studies, taken together, lead to a neurobiological understanding of the events occurring in the brain during the interaction between the therapist and his or her patient.