Infection is the most frequent complication after severe burns and remains the predominant cause of death. Burn patients may require multiple courses of antibiotics, lengthy hospitalizations, and invasive procedures that place burn patients at especially high risk for infections with multi-drug-resistant organisms (MDROs). The published literature on MDROs in burn patients was reviewed to develop a strategy for managing these infections. Within a burn unit meticulous infection prevention and control measures and effective antimicrobial stewardship can limit MDRO propagation and decrease the antibiotic pressure driving the selection of MDROs from less resistant strains. Several new antimicrobial agents have been developed offering potential therapeutic options, but familiarity with their benefits and limitations is required for safe utilization. Successful management of MDRO burn infections is supported by a multifactorial approach. Novel non-antibiotic therapeutics may help combat MDRO infections and outbreaks. Multi-drug-resistant organisms are being identified with increasing frequency in burn patients. Effective sensitivity testing is essential to identify MDROs and to direct appropriate antibiotic choices for patient treatment.