Nonsteroidal anti-inflammatory drugs (NSAIDs) are the centerpiece of pharmacologic therapy for most rheumatic disorders and related conditions, and as such are used in great numbers. These drugs are relatively safe and effective, but the pharmacokinetics of NSAIDs can be substantially altered in certain groups of patients, including the elderly and patients with renal and hepatic disease. In these patients, the risk of NSAID toxicity is increased. An understanding of NSAID pharmacokinetics in these groups can help physicians to adjust therapeutic regimens in order to limit the potentially serious complications of long-term NSAID therapy. The author discusses the age-related physiologic changes that may affect the various areas of drug pharmacokinetics and ways in which NSAIDs may interact with other drugs. Risk assessment and monitoring methods are also discussed.