Infectious diseases cause significant morbidity and mortality in immunocompromised patients. The timing and specific type of infection is often predictable and may be preventable. This chapter provides a practical overview of the broad topic of the immunocompromised host and prevention of infection, focusing on specific types of immune compromise and the types of infection associated with them. Methods of augmenting host resistance are discussed, as well as techniques to avoid exposure to potential pathogens. Topics have been chosen to include areas of care that differ from those of the immune competent patient, including isolation precautions, immunizations, augmentation of host resistance, and antimicrobial prophylaxis. National practice guidelines are cited, when available, and, where no consensus exists, practical recommendations based on available literature are provided. A systematic approach to care of the immunocompromised host, tailored to the needs of each individual patient, will reduce the risk of infection.