Opportunistic fungal infections are major causes of morbidity and mortality among immunocompromised individuals. Fungi have evolved complex and coordinated mechanisms to survive in the environment and in the mammalian host. Fungi must adapt to "stressors" in the host (including scarcity of nutrients, pH, and reactive oxygen and nitrogen intermediates) in addition to evading host immunity. Knowledge of the immunopathogenesis of fungal infections has paved the way to promising strategies for immunotherapy. These include strategies that increase phagocyte number, activate innate host defense pathways in phagocytes and dendritic cells, and stimulate antigen-specific immunity (e.g., vaccines). Immunotherapy must be tailored to specific immunocompromised states. Challenges exist in bringing promising immunotherapies from the laboratory to clinical trials.