The risk of surgical site infection (SSI) is approximately 1-3% for elective clean surgery. Apart from patient endogenous factors, the role of external risk factors in the pathogenesis of SSI is well recognized. However, among the many measures to prevent SSI, only some are based on strong evidence, for example, adequate perioperative administration of prophylactic antibiotics, and there is insufficient evidence to show whether one method is superior to any other. This highlights the need for a multimodal approach involving active post-discharge surveillance, as well as measures at every step of the care process, ranging from the operating theater to postoperative care. Multicenter or supranational intervention programs based on evidence-based guidelines, 'bundles' or safety checklists are likely to be beneficial on a global scale. Although theoretically reducible to zero, the maximal realistic extent by which SSI can be decreased remains unknown.