The medical treatment of portal hypertension has experienced marked progress in the past decade due to the production of effective portal hypertension therapy. This has been possible because of the better understanding of the pathophysiological mechanisms leading to portal hypertension. A major step forward was the introduction of beta-blockers for the prevention of bleeding and rebleeding from gastroesophageal varices. Effective therapy requires the reduction of the hepatic venous pressure gradient (HVPG) to 12 mm Hg or below, or at least by 20% of baseline values. Unfortunately, this is only achieved in 1/3-1/2 of patients. The combination therapy associated with isosorbide-5-mononitrate and propranolol or nadolol administration enhances the fall in portal pressure and increases the number of patients in whom HVPG decreases more than 20% and below 12 mm Hg. Randomized trials (RCTs) support the fact that combination therapy is more effective than propranolol or nadolol alone and better than sclerotherapy. In the treatment of acute variceal bleeding, pharmalogical therapy offers the unique advantage of permitting the provision of specific therapy immediately after arrival to hospital, or even during transferral to hospital by ambulance, since it does not require sophisticated personnel. Terlipressin has proved to be effective and to decrease mortality from bleeding. RCTs have shown that this drug is as effective and safer than emergency sclerotherapy. Therapy should be maintained for five days to prevent early rebleeding. Somatostatin is probably as effective as terlipressin.