Coccidioidomycosis is a systemic fungal infection endemic to the southwestern United States and other parts of the western hemisphere. Although producing a wide range of disorders in healthy persons, immunosuppression predisposes to especially severe disease. Thus, a knowledge of the pathogenesis of coccidioidal infections and its relation to the normal immune responses is useful to understand the diversity of problems that Coccidioides immitis may cause. Diagnosis usually requires laboratory studies such as fungal culture or specific serologic testing. Fortunately, many patients do not need to be treated for the infection to resolve. Therapy for the more severe forms of coccidioidal infection was once limited to amphotericin B but now includes azole antifungal agents. These expanded alternatives now require physicians to weigh many factors in determining the best management for specific patients.