Mucosal (oropharyngeal, esophageal, and, in women, vaginal) candidiasis is a common infectious complication in HIV-infected patients. There is a wide range of drugs to treat or suppress Candida infections. However, with the increasingly common use of fluconazole as treatment or prophylaxis in patients with relatively advanced HIV disease, mucosal candidiasis that is clinically resistant to fluconazole is increasingly recognized. Susceptibility testing for fluconazole has not been well standardized, and laboratory and clinical correlations often have been difficult to demonstrate. However, the frequency with which Candida strains resistant to fluconazole can be isolated appears to be increasing, particularly in patients with advanced HIV disease. Anecdotal results suggest that patients who fail fluconazole therapy usually do not respond to higher doses of fluconazole, but may occasionally respond to itraconazole or ketoconazole. In vitro susceptibility to these agents does not necessarily ensure clinical efficacy. Amphotericin B is usually effective initially but requires parenteral administration. However, with any therapy, relapses tend to occur and progressively recalcitrant disease often occurs, with increasing morbidity for patients. There is a clear need for studies addressing the incidence of resistance, the risk factors for its development, and more effective therapy.