Multiple emotional and cognitive factors impact on the experience of pain. This chapter will review some of the most important emotional and cognitive determinants of the pain experience as found in experimental and clinical studies with human participants. Emotional factors that may increase pain perception are anxiety, depression and anger. Positive emotions usually decrease perceived pain. The cognitive factors attention, expectancy and appraisal can either increase or decrease pain experiences depending on their specific focus and content. Many brain regions are involved in nociceptive processing and bringing pain into awareness. There are profound interconnections between areas processing sensory, emotional and cognitive information. Descending pathways from cortical areas to the midbrain and spinal levels can facilitate or inhibit spinal nociceptive information and thereby afferent nociceptive input to the brain. The underlying mechanisms of the various emotional and cognitive modulatory influences may partly overlap, but also have some unique aspects. What becomes clear is that pain is not merely a reflection of the nociceptive input, but should be considered as a complex experience shaped by psychological factors that may be unique for each individual.