The nonsteroidal anti-inflammatory drugs (NSAIDs) continue to be important for palliation of pain and decreasing inflammation and fever throughout the world. The literature over the past year has continued to broaden our understanding of the potential toxic events associated with the use of these agents. In addition, there have been interesting observations concerning their modes of action. In this article, studies describing the identification of two different isoforms of the prostaglandin synthase enzyme (cyclooxygenase) are reviewed, which might explain some of the observed differences in effects noted for the various available NSAIDs. Problems related to NSAID-induced renal dysfunction and hepatic events and gastroduodenal as well as large- and small-bowel effects of the NSAIDs are also considered.