The purpose of this review is to scrutinize the physiology of neck-shoulder pain and trapezius myalgia based on the most recent scientific literature. Therefore, systematic literature searches have been conducted. Occurrence of neck-shoulder pain, risk factors for development of neck-shoulder pain, and its work-relatedness are addressed. Furthermore, the latest information on the biochemical milieu within healthy and painful neck-shoulder muscles is reviewed. Finally diagnosis of and intervention for neck and shoulder pain are discussed.