Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options.