The measurement of cerebral blood flow (CBF) in traumatic brain injury (TBI) by means of Xenon-CT (Xe-CT) has been part of the clinical practice of several centres since 1980. Xe-CT consists of a CBF image coupled with CT which offers the possibility to associate morphologic features given by CT with functional information. Today, Xe-CT, in association with Positron Emission Tomography (PET), represents the gold standard for clinical quantitative measurement of CBF. More recently, Xe-CT has improved its potential application in the intensive care unit by means of portable CT scanner. The aim of the present review is to describe the practical experience of a single center with over five hundred Xe-CT studies obtained in more than two hundred TBI patients, to provide a method to guide the lecture of images at bedside, to present illustrative cases and to review the literature published so far on Xe-CT and TBI. The physiological and clinical variables which may be useful to explain global and regional CBF are detailed. Global CBF and its relationship with ageing, the natural time course in TBI, and the dependency on physiological variables and therapy are discussed. The coupling of global CBF with cerebral metabolic rate of oxygen (CMRO2) and the relationship of arterial venous oxygen content differences (AVDO2) with patient outcome are analyzed. Finally, the current knowledge on regional CBF found in the most important traumatic lesions (posttraumatic cerebral infarction, contusion/laceration, acute subdural hematomas, and intraparenchymal hematoma) is described.