Primary fibromyalgia syndrome (PFS) is a common form of nonarticular rheumatism with diffuse musculoskeletal aching and stiffness at multiple sites and tender points at characteristic locations. Nonmusculoskeletal "systemic" symptoms, eg, fatigue, poor sleep, irritable bowel symptoms, and chronic headaches, are also common. Although PFS is similar to myofascial pain syndrome (MPS) in that both conditions cause muscle pain and tenderness, important differences exist. Unlike PFS, muscle pain in MPS is usually local or regional, accompanied by trigger points. Unlike tender points, trigger points produce a referral pain pattern specific to each muscle. Moreover, "systemic" features of PFS are usually absent in MPS. Common and important pathologic changes in muscle in PFS are moth-eaten appearance of Type I fiber by histochemistry, and myofibrillar lysis with glycogen and mitochondria deposition by electron microscopy; inflammatory changes are absent by light microscopy. Recent investigations have shown that PFS is a characteristic clinical entity. Further controlled studies are, however, essential to establish the pathologic changes in tender muscles in PFS.