Coccidioidomycosis manifests as a variety of clinical manifestations and ranges in severity from asymptomatic exposure with resultant immunity to reinfection, to fulminant, and life-threatening disseminated disease. Primary coccidioidal pneumonia represents the most common clinical form of infection, and the incidence continues to increase. Within the endemic region, primary pulmonary coccidioidomycosis represents up to 29% of all community-acquired pneumonia emphasizing the frequency with which clinicians encounter this endemic mycosis. Chronic infection develops in 3 to 5% of patients, and almost all morbidity and mortality observed in coccidioidomycosis occur in these forms (e.g., chronic pulmonary disease, extrapulmonary manifestations). This review summarizes the ecology, epidemiology, manifestations of disease, and treatment options currently available for coccidioidomycosis.