Paracoccidioidomycosis is the most frequent endemic mycosis in South America. The infection is more prevalent in rural workers, and recent epidemiologic data suggest that changes in agricultural practices (such as a decrease in coffee plantations and an increase in sugar cane plantations) may result in a reduction in the incidence of infection. After being inhaled, Paracoccidioides brasiliensis usually causes a benign and transient pulmonary infection that may progress to an acute form or, more frequently, reactivate later as a chronic disease. The diagnosis is usually made by direct examination and culture of clinical specimens; serologic tests may be of help, especially antigen detection. The drug of choice for the chronic form is oral itraconazole, whereas patients with more severe forms may be treated with intravenous amphotericin B or sulfamethoxazoletrimethoprim. The newer azole voriconazole is also effective, and it may be a good alternative because it can be given by oral or intravenous route.