The impact of hepatic blood flow on overall metabolism is not generally appreciated but is of major consequence for homeostasis. Endocrine glands produce and secrete hormones, but for effective and rapid control of hormonal levels, a rapid turnover is required. The liver is the principal organ of clearance for a wide variety of hormones and other endogenous substances. Altered total hepatic blood flow results in altered hepatic clearance rates. The main intrinsic control of hepatic blood flow is designed to hold total hepatic blood flow steady. The liver cannot control portal venous flow (which is simply the sum of outflows of the extrahepatic splanchnic organs); therefore, to hold total blood flow steady, the hepatic artery adjusts total flow in relation to alterations in portal blood flow. This control is referred to as the hepatic arterial buffer response and it functions to regulate blood flow per se rather than nutrient or oxygen regulation. The hepatic arterial flow does not change in response to altered hepatic metabolic activity as shown by the lack of expected vascular changes with altered oxygen content of blood, altered metabolic activity induced by enzyme induction or enzyme inhibition, and altered oxygen uptake or biliary secretion. The hepatic artery is not subservient to local metabolic needs of the liver but rather is controlled in a manner that subserves the homeostatic needs of the entire body. The mechanism of the arterial buffer response is not yet clear but various hypotheses are discussed.