Pain is a subject of significant scientific and clinical interest. This has resulted both from realistic rodent models, and the publication of imaging, psychological and pharmacological studies in humans. Investigators studying rodents refer to anatomical and physiological studies in non-human primates to make their results relevant to humans. Psychophysical and pharmacological studies in humans are interpreted in terms of anatomical and physiological studies in animals; primarily evidence from rodents and cats. There are significant differences in pain mechanisms between these species and primates. Over 20 years of imaging studies have demonstrated the activation of human cortical and subcortical structures in response to painful stimuli. Interpretation of these results relies upon an understanding of the anatomy and physiology of these structures in primates. Jones, Lenz, Casey and Willis review the anatomy and physiology of nociception in monkeys and humans, and provide a firm basis for interpreting studies in humans.