Abstract Aims: During the past years, the placebo effects have changed from being regarded as a disrupting phenomenon in the clinical trials to become an important scientific topic. However, the placebo effect has attracted little attention in the medical clinics and in medical education, presumably due to limited knowledge and understanding of the value of this phenomenon. This thesis aims to investigate the psychological and the neurobiological mechanisms that may underlie the positive (placebo) and negative (nocebo) expectancy effects. The main focus will be on how these mechanisms are involved in pain modulation. Methods: Pubmed was searched for relevant literature with the search words: pain, placebo, nocebo, conditioning, expectations, learning and psychobiology in various combinations. Reference lists of selected papers were also inspected for relevant sources. Results and discussion: There are multiple mechanisms involved in these expectancy effects. Expectations and learning mechanisms seem to play a crucial role in placebo responsiveness. Classical conditioning is an important contributor for establishing unconscious expectancy effects, such as immune or hormonal responses. Expectation, on the other hand, is decisive for conscious phenomena as pain and motor performance, although it is important to point out that expectations and learning are not mutually exclusive. Social learning and individual variations in genetics, personality traits and age, among others, also plays an important role. The opioid and the dopaminergic systems are activated by placebos and expectation of reward. The -opioid antagonist, naloxone, prevents some kinds of placebo analgesia. Cholecystokinin (CCK) antagonizes both, the opioid and the dopaminergic system. The cannabinoid receptors (CB1) has also been found to play a role in the placebo responses. The prefrontal cortex seems to play an important role, but it is not essential for eliciting all types of expectancy effects. General discussion/ conclusions: It is well documented that expectations are essential for how a person experiences pain. It may therefore be valuable for clinicians and medical students to understand these fundamental and important phenomena. The expectancy effects are real phenomena, whereby psychological mechanisms regulate physiological processes that can be measured. While there are still many of unanswered questions, it is important to realize that expectations affect the patient’s healing processes, and that, therefore, the clinician should be aware of how his behaviour may elicit either placebo or nocebo responses.