Nowadays, there is compelling evidence that there is a poor relationship between the incoming sensory input and the resulting pain sensation. Signals coming from the peripheral nervous system undergo a complex modulation by cognitive, affective, and motivational processes when they enter the central nervous system. Placebo- and hypnosis-induced analgesia form two extreme examples of how cognitive processes may influence the pain sensation. With the advent of modern brain imaging techniques, researchers have started to disentangle the brain mechanisms involved in these forms of cognitive modulation of pain. These studies have shown that the prefrontal and anterior cingulate cortices form important structures in a descending pathway that modulates incoming sensory input, likely via activation of the endogenous pain modulatory structures in the midbrain periaqueductal gray. Although little is known about the receptor systems involved in hypnosis-induced analgesia, studies of the placebo response suggest that the opiodergic and dopaminergic systems play an important role in the mediation of the placebo response.