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Children born without a spleen or who have impaired splenic function, due to disease or splenectomy, are at significantly increased risk of life-threatening bacterial sepsis. The mainstays of prevention are education, immunization, and prophylactic antibiotics. The availability of conjugate 7-valent pneumococcal vaccines for use in children to age 9 years at least, as well as conjugate meningococcal C vaccine in some countries, for use beginning in infancy, appear to represent beneficial additions, but not substitutions, to previous recommendations for the use of polysaccharide 23-valent pneumococcal and quadrivalent A, C, Y, W-135 vaccines. Routine immunization against H. influenzae type b should continue with non-immunized children older than age 5 years receiving two doses 2 months apart, similar to children who have not previously received conjugate pneumococcal vaccine in infancy. Annual influenza immunization, which reduces the risk of secondary bacterial infection, is also recommended for asplenic children and their household contacts. Many experts continue prophylaxis indefinitely although prophylaxis of the penicillin allergic child remains suboptimal.