BACKGROUND Severe traumatic brain injury (TBI) requires individualized, physiology-based management to avoid secondary brain injury. Recent improvements in quantitative assessments of metabolism, oxygenation, and subtle examination changes may potentially allow for more targeted, rational approaches beyond simple intracranial pressure (ICP)-based management. The authors present a case in which multimodality monitoring assisted in decision-making for decompressive craniectomy. OBSERVATIONS This patient sustained a severe TBI without mass lesion and was monitored with a multimodality approach. Although imaging did not seem grossly worrisome, ICP, pressure reactivity, brain tissue oxygenation, and pupillary response all began worsening, pushing toward decompressive craniectomy. All parameters normalized after decompression, and the patient had a satisfactory clinical outcome. LESSONS Given recent conflicting randomized trials on the utility of decompressive craniectomy in severe TBI, precision, physiology-based approaches may offer an improved strategy to determine who is most likely to benefit from aggressive treatment. Trials are underway to test components of these strategies.