The placebo effect is the effect that follows the administration of an inert treatment (the placebo), be it pharmacological or not. It is important to understand that a placebo procedure simulates a therapy through the surrounding psychosocial context. Therefore, the study of the placebo effect is the study of the psychosocial context around the patient and its effects on the patient’s brain. The real placebo response is a psychobiological phenomenon that can be due to different mechanisms, for example expectation and conditioning. Thus, there is not a single placebo effect but many, so that we have to look for different mechanisms in different conditions and in different systems and apparatuses. Today we are beginning to understand some of the neurobiological mechanisms of the placebo response, and this knowledge may help better understand the topdown control of the incoming sensory input, like pain, and the intricate interaction between mind and body.