Management of the open abdomen following damage control laparotomy (DCL) is a critical aspect of trauma and acute care surgery, driven by the need to address life-threatening conditions while mitigating complications such as enterocutaneous fistulae (ECF), abdominal compartment syndrome, and loss-of-domain hernias. Negative Pressure Wound Therapy (NPWT) has emerged as a cornerstone in open abdomen management, offering significant advancements over historical techniques such as towel clamp closures, Bogotá bags, and vac packs. This chapter reviews the evolution of open abdomen management, emphasizing the role of Open Abdomen Negative Pressure Wound Therapy (OA-NPWT) in improving patient outcomes. OA-NPWT facilitates visceral protection, fluid management, and fascial traction, reducing 30-day all-cause mortality by up to 50%, decreasing ICU and ventilator days, and lowering overall healthcare costs. Modern resuscitation practices, including 1:1:1 protocols and direct peritoneal resuscitation (DPR), complement OA-NPWT by minimizing visceral edema and enhancing fascial closure rates. High-volume centers demonstrate superior outcomes with standardized protocols, emphasizing rapid return to the operating room every 24–48 h to mitigate complications. Despite higher initial costs, OA-NPWT reduces long-term morbidity and resource utilization, establishing it as the gold standard for open abdomen management in both trauma and acute care surgery settings.