Wound infections continue to be an important entity in terms of use of time and medical resources. Currently, the following risk factors are known to strongly predispose to wound infection: pre-existing medical illness, prolonged operative time, wound contamination, and contaminated or dirty wounds. Tissue level factors, including the local microenvironment, white cells, and cellular products that mediate inflammation, are important, and their manipulation holds promise for future therapies. For now, the judicious use of antibiotic prophylaxis and organized systems of wound surveillance are the most effective means to reduce the wound infection rate to its pathophysiologically attainable minimum.