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The in-depth study of the pathophysiology of portal hypertension is the basis for a correct medical treatment. The backward-flow theory of portal hypertension stresses the importance of increased hepatic vascular resistance, while the forward-flow theory of portal hypertension underscores generalized vasodilation, the hyperdynamic circulation and increased portal inflow. The role of expanded plasma volume has been emphasized in recent studies. The aim of drug therapy is to normalize each one of these components. Vasoconstrictor agents, i.e. vasopressin, triglycyl-lysin-vasopressin, non selective beta-blockers, somatostatin and octreotide, try to normalize the increased portal inflow and to decrease porto-collateral blood flow. Venous vasodilators, e.g. nitrates, mainly act by decreasing portal blood outflow resistance. Spironolactone has been proposed to decrease plasma volume. The use of a combination of a vasoconstrictor agent and a vasodilator or spironolactone has been proposed to increase the efficacy of medical treatment.