Infection prophylaxis in multiple trauma patients includes prophylaxis of infections due to surgery, which is the true one as well as the prophylaxis of secondary acquired infections which are more frequent, especially in case of co-existing shock. The association an aminopenicillin with a beta-lactamase inhibitor is recommended for prophylaxis of surgical infections. These antibiotics need to be administered early and in high doses, as the pharmacokinetic parameters are modified in trauma patients, with an increased volume of distribution and a shortened half-life of elimination. Prevention of secondary infection relies on a medico-surgical treatment of haemorrhagic shock. Other preventive measures, such as early enteral nutrition, selective decontamination of the digestive tract and immunotherapy, still need to prove their efficacy.