Combat-related injuries to the central nervous system (CNS) are of critical importance because of potential catastrophic outcomes. Although the overall infection rate of combat-related CNS injuries is less than 5%, if an infection develops there is a very high associated morbidity and mortality. This review focuses on the management and prevention of infections related to injuries to the brain or the spinal cord. Management strategies emphasize the importance of expert evaluation and management by a neurosurgeon. This review provides evidence-based recommendations from military and civilian data to the management of combat-related CNS injuries. Areas of focus include bacteria cultures, antimicrobial therapy, irrigation and debridement, timing of surgical care, and wound coverage. Given these recommendations are not supported by randomized control trials or adequate cohorts studies in a military population, further efforts are needed to answer best treatment strategies.