In the past 15 years, it has become increasingly evident that diverse conditions may be linked with hyposplenism and that hyposplenic individuals are susceptible to overwhelming infection, particularly by the encapsulated organisms such as pneumococci, meningococci, and Haemophilus influenzae. Identification of Howell-Jolly bodies in the peripheral blood smear is the most important clue to the diagnosis. Associated diseases include gastrointestinal disorders, hemoglobinopathies, autoimmune disorders, amyloidosis, neoplasms, circulatory disturbances, and other diseases. Hyposplenic patients should be instructed to report immediately to their physician if they suspect any infection. These patients should receive empiric treatment with antibiotics on an emergency basis at the earliest sign or symptom of infection, and they should also receive prophylactic vaccination against pneumococcal microorganisms.