Introduction. In addition to gastro-intestinal side effects, non- steroidal anti-inflammatory drugs (NSAIDs) have been associated with renal and cardiac complications. We review the mechanisms of NSAID-induced renal and cardiac toxicity and the epidemiological evidence regarding the magnitude of these problems. Methods. A Medline search was undertaken, using MESH and keyword terms, specified drug names, and renal/cardiac outcomes. The Cochrane Database was also searched. Results. Renal toxicity may manifest as acute or chronic failure and/or nephropathy, cardiac toxicity, as failure. For the most part, renal and cardiac side effects are consequences of interference by NSAIDs with prostaglandin-dependent processes;-including homeostasis and vasodilitation/constrictor balance. Based on the epidemiological evidence, NSAID-induced vasomotor renal failure is fairly uncommon, and is usually identified and treated promptly. Factors increasing the risk include old age, pre-existing renal failure, and NSAIDs with long half-lives. In patients with existing cardiac disease, NSAIDs increase the risk of failure and may account for up to 19% of failure-related hospital admissions. The risk of renal and cardiac toxicity may be highest early in the course of treatment. NSAIDs may increase mean arterial pressure by around 5mm Hg, an amount clinically significant in those with hypertension. Conclusions. NSAIDs may produce clinically significant renal and cardiac toxicity. Some of the factors increasing susceptibility may be identified easily, thereby permitting prescribers to either choose alternatives or look for evidence of harm in those most at risk.