Coccidioidomycosis is caused by a fungal pathogen native to the southwestern United States, Latin America, and South America. Fungal infection occurs after inhalation of arthroconidia, which transform into spherules. These spherules rupture to release endospores that may, in turn, cause inflammation. Increased travel of immunocompetent and immunocompromised patients has increased the frequency of coccidioidomycosis identified and treated in nonendemic areas. The primary clinical presentation of acute coccidioidomycosis is a respiratory infection similar to bacterial pneumonia about 1 to 3 weeks after exposure. Symptoms of infection include fever, headache, shortness of breath, cough, and pleuritic chest pain. Although most patients with primary coccidioidomycosis do not require treatment, patients who are severely ill, have extensive pulmonary infiltrates, or have a complement fixation titer of 1:16 or greater may benefit from treatment. Fluconazole 400 to 800 mg/d or itraconazole 400 to 600 mg/d is most commonly used for treatment; amphotericin B typically is reserved for rapidly progressing or life-threatening infections.