Determinants of placebo effects and placebo response can be considered from multiple intrinsic and extrinsic perspectives. Intrinsic factors may influence the patient and the clinician/researcher. Patient expectations and previous experiences are considered two of the major intrinsic determinants of placebo response. Other patient determinants include the neural systems under treatment/study, situational factors and reactions to the environment, and personality traits. Clinician/researcher determinants of placebo response include personality factors such as empathy, perceived expertise, the clinical relationship with the patient, and the clinician's belief in the efficacy of the treatment. Extrinsic determinants include the type of study design, influence of advertising or branding, and forces expressed by the cultural milieu. These determinants do not act in isolation, but rather form a complex interaction that ultimately impacts the promotion or deterrence of the placebo effect in clinical and research settings.