Decompressive craniectomy (DC) is used for patients with traumatic brain injury (TBI), malignant edema from middle cerebral artery infarction, aneurysmal subarachnoid hemorrhage, and non-traumatic intracerebral or cerebellar hemorrhage. The objective of the procedure is to relieve intractable intracranial hypertension and/or to prevent or reverse cerebral herniation. Decompressive craniectomy has been shown to decrease mortality in selected patients with large hemispheric infarction and to control intracranial pressure in addition to improving pressure-volume compensatory reserve after TBI. The clinical effectiveness of DC in patients with TBI is under evaluation in ongoing randomized clinical trials. There are several unresolved controversies regarding optimal candidate selection, timing, technique, and post-operative management and complications. The nature and temporal progression of alterations in cerebral blood flow, brain tissue oxygen, and microdialysis markers have only recently been researched. Elucidating the pathophysiology of pressure-flow and cerebral hemodynamic consequences of DC could assist in optimizing clinical decision making and further defining the role of decompressive craniectomy.