Amphotericin B is the treatment of choice for most deep-seated mycoses; however, doses may have to be limited because of concern over adverse effects such as nephrotoxicity. Evolving evidence suggests that the extent of amphotericin B-induced renal impairment may be modified via alteration of a normal physiologic feedback response that further contributes to changes due to direct nephrotoxicity. As such, renal impairment has a substantial theoretically preventable and reversible element. In animals exposed to amphotericin B, sodium loading interferes with this response. Mounting clinical evidence also supports the usefulness of sodium supplementation to prevent as well as to reverse amphotericin B-induced nephrotoxicity. At this time, the use of sodium supplementation (eg, intravenous saline and/or ticarcillin disodium, which contains 5.2 mEq of sodium per gram of drug) along with avoiding dehydration appears to be a safe and effective means of reducing the risk of nephrotoxicity associated with amphotericin B administration; however, it is not known whether renal changes can be entirely prevented. These preliminary observations merit confirmation in a prospective, randomized clinical trial.