Until recently, culture, microscopy, and serology have been the available methods for the diagnosis of coccidioidomycosis. While Coccidioides is frequently isolated by culture, special precautions must be taken because of the risk of laboratory infection and because Coccidioides is on the Select Agent list. Serology is useful but the sensitivity remains lower than desired. A commercially available test for coccidioidal galactomannan antigenuria now exists and appears useful for immunocompromised hosts with severe disease. Polymerase chain reaction assays targeting specific coccidioidal genes have demonstrated utility but are not commercially available. Moreover, their sensitivity and the best sample type remain unestablished.