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Acute abdominal compartment syndrome (ACS) is a clinical entity that develops from a progressive, acute increase in pressure within the confined space of the abdominal cavity from a multitude of etiologies. This increase in intra-abdominal pressure (IAP) impacts multiple organ systems in a graded fashion due to differential susceptibilities. While the classic renal, pulmonary, and cardiovascular signs are seen with marked elevations in IAP, we now know that the gut is most sensitive to increases in IAP and develops evidence of end-organ damage earlier in the development of ACS. Furthermore, intracranial derangements with ACS are now well described. Treatment involves expedient decompression of the abdomen, without which the syndrome of end-organ damage and reduced oxygen delivery may lead to the development of multiple organ failure and ultimately death. The scenarios of multiple trauma, hemorrhage with massive volume resuscitation, and/or protracted operation are where ACS is most frequently encountered. However, knowledge of ACS is also essential for the management of critically ill pediatric patients and intensive care patients with acute medical illnesses. The role of intra-abdominal hypertension (IAH) in the etiology of necrotizing enterocolitis, central obesity comorbidities, and preeclampsia/eclampsia remains to be fully elucidated. This article reviews the experimental background, organ system pathophysiology, diagnosis, and treatment of ACS with emphasis on the latest concepts in the literature as they apply to critically ill patients.