The human body has multiple systems in place to aid in preventing the development of infection in the host. When these systems are disrupted (e.g., through comorbidities, healthcare therapy, or intrinsic defect), the host cannot not efficiently fight infection. Certain pathogens that do not affect or cause only mild illness in the immunocompetent host cause significant morbidity and mortality in immunocompromised patients. The specific types of infection of particular concern for these patients are 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 compromised immunity and the types of infection associated with them, strategies to improve host resistance, and methods for minimizing exposure to pathogens.