Infections of the upper respiratory tract are a major source of morbidity and mortality in the immunocompromised host. The risks and types of infections are dictated by the specific immune defects present in the patient. Infections may involve virtually any of the structures in the upper respiratory tract, including the oral cavity, pharynx, larynx, trachea, ear, and sinuses. Infections may be complicated by abscess formation or invasion of critical central nervous system or neck space structures. Physicians must maintain a high index of clinical suspicion for upper respiratory tract infections, especially because they may present in an atypical fashion or be caused by unusual organisms in immunocompromised patients. For many of these infections, prompt initiation of appropriate antimicrobial therapy may be life saving. Prophylactic use of antibiotics, antifungal drugs, or antiviral agents is indicated in specific groups of immunocompromised patients.