Viability of the cerebral parenchyma is dependent on cerebral blood flow (CBF), which is usually kept in a very narrow range due to efficient autoregulation processes and can be altered in a variety of pathological conditions. An accurate method allowing for a quantitative assessment of regional cerebral blood flows (rCBF) and available for the routine clinical practice would, for sure, greatly contribute to improving the management of patients with cerebrovascular diseases. Different imaging techniques are now available to evaluate rCBF: positron emission tomography; single photon emission CT; stable-xenon CT; perfusion CT; and perfusion MRI. Each of these imaging techniques uses an indicator, with specific biological properties, and is supported by a model, which consists of a few simplifying assumptions, necessary to state and solve the equations giving access to rCBF. The obtained results are more or less reliable, depending on whether modeling hypotheses are fulfilled by the used indicator. The purpose of this article is to review the various supporting models in the assessment of rCBF, with special emphasis on perfusion CT studies at low injection rates and on iodinated contrast material used as an indicator.