Introduction: Coccidioidomycosis is an endemic fungal infection caused by the soil-dwelling fungi, Coccidioides species. Coccidioidal infections may be asymptomatic in up to two-thirds of infected persons. Pulmonary coccidioidomycosis is the most common form of symptomatic infection. Fluconazole is the antifungal agent typically used to treat pulmonary coccidioidomycosis. Other azoles and amphotericin B products may be prescribed to treat nuanced aspects of coccidioidomycosis.Areas covered: This review discusses current literature regarding medical treatment options, including the various triazoles and amphotericin B products. In addition, we discuss uncomplicated and complicated pulmonary infections and their sequelae and the approach to managing coccidioidomycosis in certain populations of patients, such as pregnant women, transplant recipients, individuals infected with human immunodeficiency virus, and recipients of tumor necrosis factor- inhibitors.Expert commentary: Symptomatic coccidioidomycosis can present physicians with a number of challenges, including the lack of sensitivity and specificity of diagnostic tests and lack of a standard treatment approach for all patients with the infection. Ongoing and future clinical trials will determine the optimal diagnostic, therapeutic, and prophylactic approaches, particularly for patients with comorbid conditions.