The complications of portal hypertension are totally prevented if hepatic venous pressure gradient is decreased below 12 mm Hg. Besides, if this target is not achieved, a 20% decrease in portal pressure from baseline levels offers an almost total protection from variceal bleeding. This sets the rationale for drug therapy to reduce portal pressure in portal hypertension. Pharmacological therapy to decrease portal pressure includes vasoconstrictors to decrease portal blood inflow, vasodilators to decrease hepatic resistance, and combination therapy. Oral agents, such as b-adrenergic blockers and organic nitrates, are used for long-term prevention of variceal bleeding, while parenteral agents, such as somatostatin (and analogues) and terlipressin, are used for the treatment of acute variceal bleeding.