Selective inhibitors of cyclooxygenase (COX)-2 afford relief from pain and inflammation. They could also prove useful in the chemoprevention of cancer and are being investigated in a range of neurological diseases. This novel class of drug is less likely to cause gastric ulceration than traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, plausible mechanisms have been proposed whereby COX-2 inhibitors could cause thrombosis or renovascular hypertension in patients predisposed to these conditions. The limited data available with structurally distinct inhibitors in relevant populations are consistent with this possibility, although these might be partly explained by a cardioprotective effect of the tNSAID naproxen. This article will review the role of COX-2 inhibitors in a number of indications, including cardiovascular disease, hypertension and atherosclerosis.