There is a growing body of evidence suggesting imaging biomarkers to select patients with traumatic brain injury (TBI) for therapies, and to monitor the effects of these treatments. In this setting, advanced neuroimaging techniques such as perfusion-CT (PCT) can offer more clinically relevant pathophysiologic information than purely structural imaging such as conventional noncontrast CT. Patients with altered brain PCT results might be considered for more aggressive and early treatment to prevent intracranial hypertension, whereas patients with preserved brain perfusion might benefit from less invasive treatment. From a clinical trial perspective, better stratification of the patient population, and the use of advanced neuroimaging as a biomarker for response to intervention, could be expected to significantly reduce the number of patients required to assess a treatment effect and, therefore, expedite the clinical trial process. This article reviews the fundamental of perfusion-CT technique and its application to TBI.