Portal hypertension is characterised by alterations in the splanchnic and systemic circulation associated with the development of portosystemic collateral channels, the most important of which are found in lower oesophagus and stomach. Bleeding from these gastro-oesophageal varices represents the major clinical complication and over the last decade there has been considerable interest in the pharmacological management of this condition. The factors underlying the development and maintenance of portal hypertension and the pathogenesis of variceal rupture are as yet not fully understood. Whilst an increase in portal vascular resistance, as a consequence of liver disease, appears to be the primary event in the majority of cases, increasing attention has focused on the potential importance of enhanced circulating levels of vasoactive compounds coupled with a proposed reduction in vascular sensitivity to endogenous vasoconstrictors. Consequently, portal hypertension is now being more widely considered as a multi-organ disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development and maintenance of portal hypertension and considers the pathogenesis of variceal bleeding.