The discovery of the isoenzymes cyclooxygenase-(COX-) 1 and COX-2 led to the development of newer nonsteroidal anti-inflammatory drugs (NSAIDs) designed to block COX-2, such as rofecoxib, celecoxib, and valdecoxib. Because of the specificity of COX-2 expression, COX-2 inhibitors have the potential to reduce the risk of gastrointestinal bleeding experienced with the use of classic NSAIDs. With their crucial role in the control of inflammation, the COX-2 agents originally were marketed for the treatment of rheumatoid and osteoarthritis. However, promising new indications for COX-2 agents in the prevention and treatment of cancer are under investigation. The role of aberrant COX-2 expression in the development of cancer has been studied most widely in patients with colon cancer and adenomas. Recent studies suggest that COX-2-derived prostaglandins may play an important role in tumor viability, growth, and control of metastasis. Possible new indications for the use of COX-2 inhibitors to prevent and treat cancers may be monumental. However, therapy with these agents is not without risk. Oncology nurses must be aware of the potential problems inherent in the use of COX-2 as well as COX-2 agents for chemoprevention in certain cancers.