PURPOSE OF REVIEW Intracranial pressure (ICP) control is a mainstay of traumatic brain injury (TBI) management. However, development of intracranial hypertension (ICH) may be affected by factors outside of the cranial vault in addition to the local effects of the TBI. This review will examine the pathophysiology of multiple compartment syndrome (MCS) and current treatment considerations for patients with TBI given the effects of MCS. RECENT FINDINGS Elevated intra-abdominal pressure (IAP) is associated with ICP elevation, and decompressive laparotomy in patients with concurrent elevations in IAP and ICP can reduce ICP. Elevated intrathoracic pressure may be similarly associated with ICP elevation, although the ideal ventilator management strategy for TBI patients when considering MCS is unclear. SUMMARY In MCS, intracranial, intrathoracic and intra-abdominal compartment pressures are interrelated. TBI patient care should include ICP control as well as minimization of intrathoracic and intra-abdominal pressure as clinically possible.