Invasive fungal infections represent an often overlooked but frequently life-threatening complication for critically ill patients. Clinical presentations range from relatively innocuous superficial skin infection to invasive disease resulting in acute respiratory distress syndrome (ARDS), fungemia, and meningoencephalitis. Early detection and rapid initiation of antifungal treatment are key to successful management of infection. Diagnosis relies on high clinical suspicion. Growth in culture media or histopathological analysis remains the gold standard for diagnoses, though it is often delayed. Testing modalities including fungal serology, fungal antigen testing, and polymerase chain reaction (PCR) assays can expedite putative diagnosis. Primary treatment options include the antifungal classes of polyenes, azoles, and echinocandins as well as surgical excision and debridement when indicated. This chapter delineates the three major clinical groups of fungal infection, clinical evaluation, and treatment guidelines for each.