People with asplenia are at risk for infections due to many causative agents, mainly Streptococcus pneumoniae. Among adults, splenectomy is the most frequent etiology of hyposplenism followed with chronic hematological and connective diseases. Physiopathology of the immunologic impairment due to hyposplenia is multifactorial. Physicians and even patients must be aware of overwhelming sepsis occurring on these conditions. The prognosis of these life-threatening infections is related to the precocity of the treatment onset. These infections, mainly due to S. pneumoniae (50-90% of cases) could be prevented with appropriate precautions. Patients presenting with asplenia must be largely vaccinated against these infectious agents: S. pneumoniae, Haemophilus influenzae b, and possibly Neisseiria meningitidis. Oral phenoxymethylpenicillin seems to be the simplest chemoprophylaxis (despite the global increase of pneumococcal strains with reduced susceptibility). Duration of treatment following splenectomy is discussed: The French medicine agency (AFSSAPS) recommends a 2-year treatment after surgery and for patients having functional hyposplenism (persistency of Howell-Jolly bodies) and/or associated immunodeficiency. Despite these prevention policies, the patient must be informed of the risk of very severe infection.