Anti-inflammatory agents and myorelaxants are the cornerstone of pharmacologic management of musculoskeletal disease. Combinations of these drugs are recommended for the treatment of muscle spasm and injury, whereas anti-inflammatory agents alone are used to treat inflammatory pain such as rheumatoid arthritis. Choosing the most effective regimen for patients with pain can be difficult. This article reviews the pharmacology and clinical use of these agents to define how to use these medications better.