Coccidioidomycosis is endemic only in the Western Hemisphere, mainly in southern Arizona, New Mexico, Texas, and much of central and southern California, and in small areas in South American countries, including Argentina, Brazil, Colombia, Paraguay, and Venezuela. It is highly endemic in northern Mexico. The organism grows in soil in a semiarid, geographically restricted region, the Lower Sonoran Life Zone. Two nearly identical species cause coccidioidomycosis: Coccidioides immitis and Coccidioides posadasii. Upon inhalation, the fungus enters the lungs and converts to the tissue parasitic phase, which consists of alternating spherules and endospores. Infection can be asymptomatic or can cause flulike symptoms, meningitis, or skin, bone or joint manifestations. Diagnosis and treatment are also reviewed.