Regional soft-tissue complaints are commonplace, and they usually relate to a disease process, such as strain, inflammation or degeneration of a muscle, tendon or related muscle-tendon unit. The clinical features and investigations of the causative processes of these complaints are characteristic, and outcomes to treatments are usually predictable and satisfactory. Regional pain syndromes are different: these syndromes present with regional pain and tenderness, and other sensory symptoms unaccounted for by a simple musculoskeletal mechanistic explanation. Approved classification criteria for regional pain syndromes are lacking, and these syndromes are poorly understood and frequently misdiagnosed. Regional pain syndromes often occur after injury and overlap extensively with other musculoskeletal pain syndromes, in terms of clinical signs and symptoms. The clinician and patient are often confused about the nature of the problem and routine treatments directed to putative tissue damage will fail. Review of the epidemiology of regional pain syndromes combined with knowledge of other similar pain syndromes has enabled an evolving understanding of the condition. The musculoskeletal and central nervous systems both contribute to regional pain syndromes, through spine-related pain mechanisms and central sensitization, respectively. The patient's emotional state, particularly the effect on pain modulation, links these two systems.