Chronic nonmalignant pain is a major burden on the health care system in the United States. Frequently, nonsteroidal antiinflammatory drugs (NSAIDs) are used to assist in the management of various chronic pain syndromes. Although evidence is accumulating on the potential toxicities associated with NSAIDs, clear recommendations are lacking to guide the appropriate use of these drugs. Equivocal data, especially with respect to cardiovascular risk, further confuse a clear treatment pathway when assessing pharmacotherapy. Originally, cyclooxygenase selectivity appeared to be a determining factor in choosing an agent because of the presumed lack of effect on the cardiovascular and gastrointestinal renal systems. This theory, however, was recently dispelled. To provide guidance on the selection of an NSAID for various chronic pain syndromes, members of the Ambulatory Care, Cardiology, and Pain and Palliative Care Practice and Research Networks of the American College of Clinical Pharmacy evaluated evidence-based use of NSAIDs for frequently encountered pain syndromes, with special focus on the adverse effects of this class of agents.