The percentage of combat wounds involving the eyes, maxillofacial, and neck regions reported in the literature is increasing, representing 36% of all combat-related injuries at the start of the Iraq War. Recent meta-analysis of 21st century eye, maxillofacial, and neck injuries described combat injury incidences of 8% to 20% for the face, 2% to 11% for the neck, and 0.5% to 13% for the eye and periocular structures. This article reviews recent data from military and civilian studies to support evidence-based recommendations for the prevention of infections associated with combat-related eye, maxillofacial, and neck injuries. The major emphasis of this review is on recent developments in surgical practice as new antimicrobial studies were not performed. Further studies of bacterial infection epidemiology and postinjury antimicrobial use in combat-related injuries to the eyes, maxillofacial, and neck region are needed to improve evidence-based medicine recommendations. This evidence-based medicine review was produced to support the Guidelines for the Prevention of Infections associated with Combat-related Injuries: 2011 Update contained in this supplement of Journal of Trauma.