The authors report on the use of combination intravenous and inhaled colistin therapy in 2 patients with major burns admitted to an American Burn Association-verified burn center during a multidrug-resistant (MDR) Acinetobacter baumannii outbreak. Both patients had documented, culture-proven MDR Acinetobacter ventilator-associated pneumonia and bacteremia leading to sepsis. Both patients were successfully extubated and subsequently discharged from hospital. In this article, the authors provide the timeline of events and treatments that were used in these 2 cases. Combination intravenous and inhaled colistin therapy may be a valuable tool against MDR Acinetobacter infections.