Overwhelming post-splenectomy infection (OPSI) is a long-term risk in asplenic patients, which may be controlled by appropriate preventive measures. Specific guidelines have been developed to reduce its incidence. These guidelines include immunizations, antibioprophylaxis, and education. Immunizations against S. pneumoniae, N. meningitidis, Hamophilus influenzae, and influenza should be administered. Antibioprophylaxis during 2 to 5 years following splenectomy in children, and 2 years in adults is recommended. Furthermore, long-term education is mandatory. Application of preventing measures is effective and patient's education remains the cornerstone of prevention.