In the last decade, knowledge regarding mechanisms involved in the pathogenesis of portal hypertension has taken unprecedented levels. However, many aspects still remain to be elucidated. Portal hypertension is primarily caused by an increase in resistance to portal outflow and secondly by an increase in splanchnic blood flow. In a later phase, these changes lead to a hyperdynamic circulation with increased cardiac output and decreased systemic vascular resistance and perfusion pressure. Regional alterations in vasoreactivity (vasodilation and vasoconstriction) play a central role in the pathophysiology of portal hypertension by contributing to increased intrahepatic resistance, hyperdynamic circulation, and expansion of the collateral circulation. Among vasoactive substances activated in portal hypertension, nitric oxide (NO) is considered as the most important vasodilator. Endothelin-1 and cyclooxygenase-derived prostaglandins are the foremost vasoconstrictor factors. The imbalance between the hyperresponsiveness and overproduction of vasoconstrictors and the hyporesponsiveness and impaired production of vasodilators are the main responsible of the increased vascular one in the sinusoidal area of the liver. In addition to an imbalance in vasoactive substances, a major role has been attributed to activated hypercontractile hepatic stellate cells which cause vascular remodelling as an adaptive response to the changed balance in vasoactive substances. The present paper aims to elucidate on available knowledge and novel mechanisms gathered over the last years with regard to cirrhotic portal hypertension and the increased intrahepatic vascular resistance in particular.