The most frequent cause of portal hypertension is liver cirrhosis, and many of lethal complications of cirrhosis such as ascites and gastroesophageal variceal hemorrhage are related to portal hypertension. This chapter provides knowledge of the biology of portal hypertension with a focus on cellular and molecular events in different segments of vasculatures that contribute to the development and perpetuation of portal hypertension and the subsequent development of hyperdynamic circulatory syndrome. Angiogenesis, or the process of new blood vessel formation from pre‐existing vascular beds, has been implicated in portal hypertension. The study of intrahepatic portal hypertension is evolving to include platelet activation and thrombosis as crucial factors for its pathophysiology. Because of the disparate conditions of vascular tone in the intrahepatic and extrahepatic circulations, the organ/tissue or cell‐specific modulation of vasodilator or vasoconstrictor molecules is of paramount importance for therapeutic purposes.