Measurement of hepatic blood flow is fundamental to understanding hepatic physiology and biochemistry, quantitating drugs metabolized in the liver, and describing pathophysiologic states such as portal hypertension. However, the dual blood supply, altered handling of labels during disease states, and the relative inaccessibility of the portal system have made precise measurements of hepatic blood flow difficult. A variety of techniques can be utilized in both laboratory animals and patients; the more invasive techniques are generally available for animal studies, while semi-invasive and noninvasive methodologies yield information from patients. Each method has its inherent strengths and weaknesses, and may be utilized in a particular circumstance to accurately assess hepatic blood flow. It is therefore critical to select a measurement technique which yields the desired accuracy without interfering with the physiologic conditions under study. The methodology is presently available to achieve this end.