Severe fungal infections have become increasingly common over the past 10 years, largely due to the greater number of immunocompromised patients, such as those infected with HIV and those undergoing immunosuppressive therapy for malignancies. Between 60% and 80% of people with AIDS, for example, develop at least one fungal infection. Other predisposing factors for these infections include mechanical defects such as indwelling catheters, surgery, and burns. Candidiasis, aspergillosis, cryptococcoses, coccidioidomycosis, and histoplasmosis are among the fungal infections most commonly encountered in the clinical setting. Diagnosis is often elusive and treatment difficult. Amphotericin B has been the standard therapy for most life-threatening fungal infections for almost three decades but has significant drawbacks, including severe adverse reactions. Other systemic antifungal agents have proved useful in certain situations. Fluconazole, a new broad-spectrum agent, has shown particular promise in the treatment of candidiasis and cryptococcal meningitis.