The frequency of life-threatening fungal infections has increased dramatically over the past few decades. For more than 30 years amphotericin B has been the standard treatment for systemic and deep-seated fungal infections, primarily because of its broad spectrum of activity. Its usefulness is limited by a relatively high frequency of significant adverse events including infusion-related reactions and nephrotoxicity. In an effort to overcome these side effects, a number of lipid-based formulations were developed, each with its own composition and pharmacokinetic behavior. The clinical significance of these differences is unknown. Available clinical data suggest the formulations have a reduced propensity for causing nephrotoxicity. However, considering limited efficacy data, they should be reserved as second-line therapy for patients who cannot tolerate or fail an adequate trial of conventional amphotericin B or cannot benefit from other antifungal agents.