Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time-activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time-activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time-activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time-activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic (18)F-FDG PET/CT recording. Later, steady-state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, (18)F-FDG and (11)C-palmitate.