Amphotericin B has a broad spectrum of action that includes most of the major fungal pathogens of man. This drug binds to the membrane sterols of fungal cells, causing impairment of their barrier function and loss of cell constituents. Metabolic disruption and cell death are consequent upon membrane alterations. Investigations of the sterol content of mutant strains of Candida albicans and Cryptococcus neoformans has demonstrated that resistance is often associated with alterations in membrane sterol composition. Treatment failure due to the development of amphotericin B resistance is an uncommon problem. It has tended to occur in patients receiving treatment with cytotoxic drugs. Interactions between amphotericin B and a number of other antimicrobial drugs have been observed in tests in vitro and in vivo. However, apart from one report that the combination with flucytosine is superior to amphotericin B on its own in the treatment of cryptococcal meningitis, there have been no controlled trials to support the use of drug combinations in human infections.