Decompressive craniectomy (DC) involves the removal of a portion of the skull in the setting of life threatening brain edema or potentially uncontrollable intracranial pressures. Often performed on an emergent basis, evaluation and arrangement for DC should be swift and decisive. However, the evidence base for DC in the wide range of conditions for which it is currently performed is still developing. The procedure is associated with a number of complications and ethical considerations; thus, its place in contemporary practice remains controversial. While randomized trials conducted in the last decade have provided valuable data on the indications, eligibility criteria, and outcomes for DC in the treatment of traumatic brain injury and malignant middle cerebral artery infarction, important outstanding issues continue to complicate the decision to pursue DC on an individual case basis and in the number of other clinical settings presenting with brain edema and intracranial hypertension. In this review, we present the existing evidence and remaining questions regarding DC in various neurologic conditions including traumatic brain injury, ischemic stroke, subarachnoid hemorrhage, spontaneous intracerebral hemorrhage, encephalitis, and others. We also discuss perioperative considerations and ethical issues likely to be encountered by clinicians caring for patients and families who are considering or have undergone DC.