Acute renal failure (ARF) in patients in the ICU is associated with a high mortality. Drug-induced renal dysfunction is an important, yet often overlooked, cause of ARF in this patient population. A drug use evaluation at the authors’ institution, to assess the prescribing patterns of potential nephrotoxins in the adult and pediatric ICUs, found that antibiotics (aminoglycosides, amphotericin B, penicillins, cephalosporins, acyclovir), nonsteroidal anti-inflammatory drugs, contrast dye, and various other nephrotoxic medications are used widely in all of the ICUs. By focusing on several commonly prescribed classes of nephrotoxic medications in the ICU, this article reviews the general mechanisms of drug-associated renal dysfunction.