Certain gaseous tracers, characterized by being metabolically inert and possessing the capability of diffusing rapidly between blood and tissue, have been used for many years to derive estimates of cerebral blood flow in vivo, as well as in the animal laboratory. The work of Kety and Schmidt (1945), who developed the nitrous oxide technique for the determination of cerebral blood flow in humans, has provided the foundation for a range of techniques for the measurement of total and regional cerebral blood flow, many of them highly sophisticated and employing a wide spectrum of physical principles. As these techniques found their way into clinical practice, it was inevitable that pressure should build up to limit the invasive nature of the investigations. Thus from the xenon-133 intracarotid artery injection technique, we have seen the development of inhalation and intravenous (iv) injection methods. Furthermore, the development and rapid acceptance of X-ray CT scanning into the diagnostic armamentarium has led to blood flow determinations that rely on the use of stable xenon as an enhancement agent, whereas the introduction of positron emission tomography gave rise to three-dimensional assessment of regional cerebral blood flow and metabolism utilizing short-lived radionuclides such as oxygen-15.