Surgical site infections (SSI) are very common, and represent more than 20% of all hospital-acquired infections. SSIs are associated with a higher mortality, as well as to an extended hospital stay and costs, depending on the surgical procedure and type of SSI. Advances in control practices for these infections include improvement in operating room ventilation, sterilization methods, barriers, and surgical techniques, as well as in surgical antimicrobial prophylaxis. For the latter, the antimicrobial agent should: be active against the most common pathogens, be administered in an appropriate dosage and in a time frame to ensure serum and tissue concentrations over the period of potential contamination, be safe, and be administered over the shortest effective time period to minimize adverse events, development of resistances, and cost.