A seminal advance in the prevention of colon cancer has been the observation that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the incidence of and mortality from colon cancer by about half. Among current efforts to overcome the side effects of NSAIDs, an important limitation for their application as chemopreventive agents, is the synthesis of nitric oxide-releasing NSAIDs. These novel compounds may display greater safety and greater efficacy compared to their parent traditional NSAIDs and thus hold significant promise as chemopreventive agents against human colon cancer. In this review we discuss salient features of their pharmacology, in vitro and animal data pertaining to colon cancer, their mechanisms of action, and assess their potential in the chemoprevention of colon cancer.