Severe traumatic brain injury remains a significant cause of mortality and morbidity worldwide. The use of therapeutic interventions such as hypertonic saline administration and decompressive craniectomy have solid foundations and can improve outcomes, although questions remain about patient selection, optimal timing, and comparisons to other treatments. Hypothermia, while having promise, has not definitively been shown to benefit patients with traumatic brain injury, although clinical trials are underway. The use of β-blockers in traumatic brain injury has been proposed as a neuroprotective measure, but data are lacking to support widespread clinical use. Brain tissue oxygenation monitoring is gaining widespread acceptance as a safe tool to provide additional information both to guide therapeutic interventions and to further elucidate mechanisms of secondary brain injury. Evidence is also mounting that guided therapy using brain tissue oxygenation in addition to intracranial pressure and cerebral perfusion pressure monitoring leads to better outcomes after traumatic brain injury.