Coccidioidomycosis is usually acquired by inhalation of Coccidioides immitis in certain areas of the Western Hemisphere. However, the disease may occur far away in individuals who have visited or lived in, then departed from, the endemic areas. The disease which can affect normal and immunocompromised individuals, has many manifestations resembling those of many diseases. The diagnosis is usually not difficult and can be accomplished by histopathological, cultural, and serological methods. Therapy can be surgical and/or medical. The latter can make use of parenteral amphotericin B and its lipid-complex, or the azoles ketoconazole, fluconazole, and itraconazole. However coccidioidal meningitis, coccidioidal arthritis, and acute coccidioidal respiratory insufficiency pose significant challenges to the available therapy.