The diagnosis of fungal disease is a challenge that requires diligent attention to history and clinical signs as well as an astute ability to interpret laboratory data. Because fungal disease can mimic other infectious and neoplastic diseases in clinical presentation, the clinician has to be aware of fungal diseases common locally as well as in other regions of the country. A global approach to the diagnosis of fungal disease that correlates clinical signs as well as physical examination, clinical pathology, and histopathology findings with serology, culture, and the newer immunohistochemical and molecular techniques, where available, is the best approach to optimize the identification of the underlying agent.