An immunosuppressed patient is unable to mount the normal, co-ordinated immune response to trauma and infection. Respiratory failure or sepsis are the commonest reasons for immunosuppressed patients to require ICU admission. Respiratory failure can result from multiple simultaneous pulmonary processes, both infectious and noninfectious. As a consequence of both the primary illness and its treatment, patients with malignancies are prone to episodes of neutropenia. Despite rigorous screening, transmission of infection from the donor organ can occur. With the advent of highly active antiretroviral therapy (HAART), the prognosis of patients with HIV and AIDS has improved enormously. Splenic macrophages have an important filtering and phagocytic role in removing bacteria and parasitized red cells from the circulation. Life-threatening infection is a major long-term risk post splenectomy. Most serious infections are due to encapsulated bacteria. Lifelong antibiotics should be offered to all patients; however, the first 2 years post splenectomy appear especially important.