Decompressive craniectomy is widely used to treat intracranial hypertension following traumatic brain injury (TBI). Two randomized trials are currently underway to further evaluate the effectiveness of decompressive craniectomy for TBI. Complications of this procedure have major ramifications on the risk-benefit balance in decision-making during evaluation of potential surgical candidates. To further evaluate the complications of decompressive craniectomy, a review of the literature was performed following a detailed search of PubMed between 1980 and 2009. The author restricted her study to literature pertaining to decompressive craniectomy for patients with TBI. An understanding of the pathophysiological events that accompany removal of a large piece of skull bone provides a foundation for understanding many of the complications associated with decompressive craniectomy. The author determined that decompressive craniectomy is not a simple, straightforward operation without adverse effects. Rather, numerous complications may arise, and they do so in a sequential fashion at specific time points following surgical decompression. Expansion of contusions, new subdural and epidural hematomas contralateral to the decompressed hemisphere, and external cerebral herniation typify the early perioperative complications of decompressive craniectomy for TBI. Within the 1st week following decompression, CSF circulation derangements manifest commonly as subdural hygromas. Paradoxical herniation following lumbar puncture in the setting of a large skull defect is a rare, potentially fatal complication that can be prevented and treated if recognized early. During the later phases of recovery, patients may develop a new cognitive, neurological, or psychological deficit termed syndrome of the trephined. In the longer term, a persistent vegetative state is the most devastating of outcomes of decompressive craniectomy. The risk of complications following decompressive craniectomy is weighed against the life-threatening circumstances under which this surgery is performed. Ongoing trials will define whether this balance supports surgical decompression as a first-line treatment for TBI.