The recent release of the selective cyclooxygenase-2 (COX-2) enzyme inhibitors for the treatment of various inflammatory disorders and pain syndromes has been associated with a clear-cut decrease in adverse gastrointestinal effects. The nephrotoxic effect of selective COX-2 inhibitors has not yet been firmly established. We report a case of reversible acute renal failure due to rofecoxib treatment in an elderly patient with several risk factors associated with traditional nonselective nonsteroidal anti-inflammatory drug (NSAID)-related nephrotoxicity. It is prudent to approach therapy with selective COX-2 inhibitors cautiously and in a fashion similar to traditional NSAID therapy for patients with risk factors that induce prostaglandin-dependent renal function.