Over the last decade coccidioidomycosis, a fungal infection endemic to the desert Southwest of the United States, has gained national prominence. This review summarizes recent advances in the clinical understanding of this disease. Immunosuppressive therapy and infection with the human immunodeficiency virus are recognized risk factors for the development of severe, progressive disease. Although relatively uncommon, extrapulmonary dissemination of Coccidioides immitis can lead to chronic infection of the skin, bones, and meninges. Culture and histologic examination are important in establishment of the diagnosis, but serologic tests remain both diagnostically and prognostically useful. Treatment is problematic. Coccidioidomycosis is an unpredictable disease, and assessments of drug efficacy are difficult. Ketoconazole is challenging amphotericin B as the preferred treatment for some manifestations. However, many of the adverse effects of ketoconazole have only recently been recognized. Newer antifungal agents, such as fluconazole and itraconazole, hold promise for the future.