Humans have a broad array of host defense mechanisms against fungal invasion. Most serious mycoses occur in patients who have defects in one or more of these defenses. Defense mechanisms not related to the immune system include barriers created by the skin and mucous membrane, competition from the normal indigenous bacterial flora, mucociliary clearance mechanisms, and fungistatic products in serum such as metal chelators. Among the immune mechanisms, activation of the complement system and generation of an antibody response facilitates recognition of fungi by specific receptors on immune cells. Quantitative and qualitative disorders of phagocytic function predispose patients to the development of invasive aspergillosis and candidiasis. Impairment of cell-mediated immunity predisposes patients to cryptococcosis, histoplasmosis, coccidioidomycosis, and mucocutaneous candidiasis. An overexuberant inflammatory response to fungal antigens can result in morbidity and mortality because of damage to host tissues. Knowledge of the type of immunocompromise that is afflicting a patient enables the clinician to predict which mycoses the patient is likely to have and to which the patient is predisposed.