Portal hypertension, a major complication of cirrhosis, is caused by both increased portal blood flow and augmented intrahepatic vascular resistance. Even though the latter is primarily caused by anatomical changes, it has become clear that dynamic factors contribute to the increased hepatic vascular resistance. The hepatic sinusoid is the narrowest vascular structure within the liver and is the principal site of blood flow regulation. The anatomical location of hepatic stellate cells, which embrace the sinusoids, provides a favorable arrangement for sinusoidal constriction, and for control of sinusoidal vascular tone and blood flow. Hepatic stellate cells possess the essential contractile apparatus for cell contraction and relaxation. Moreover, the mechanisms of stellate cell contraction are better understood, and many substances which influence contractility have been identified, providing a rationale and opportunity for targeting these cells in the treatment of portal hypertension in cirrhosis.