Chronic musculoskeletal pain results from a complex interplay of mechanical, biochemical, psychological, and social factors. Effective management is markedly different from that of acute musculoskeletal pain. Understanding the physiology of pain transmission, modulation, and perception is crucial for effective management. Pharmacologic and nonpharmacologic therapies such as psychotherapy and biofeedback exercises can be used to manage chronic pain. Evidence-based treatment recommendations have been made for chronic pain conditions frequently encountered by orthopaedic surgeons, including low back, osteoarthritic, posttraumatic, and neuropathic pain. Extended-release tramadol; select tricyclic antidepressants, serotonin reuptake inhibitors, and anticonvulsants; and topical medications such as lidocaine, diclofenac, and capsaicin are among the most effective treatments. However, drug efficacy varies significantly by indication. Orthopaedic surgeons should be familiar with the widely available safe and effective nonnarcotic options for chronic musculoskeletal pain.