Variceal hemorrhage still carries a high mortality and a high risk of recurrence. Esophageal varices bleed rarely with a porto-systemic pressure gradient below 12 mmHg; pharmacotherapy, thus, aims at lowering the pressure gradient below this critical threshold. Conceptually, this can be achieved by decreasing portal-venous inflow (via lowering cardiac output and/or increasing splanchnic-arteriolar vasoconstriction) or by decreasing portal-venous resistence (via portal vasodilation). In acute variceal bleeding, easily applicable pharmacotherapy with terlipressin plus nitroglycerin, probably also with octreotide, can help to stabilize the patient and to buy time until diagnostic endoscopy and treatment by sclerotherapy or variceal band ligation. For pharmacotherapeutic secondary prophylaxes of variceal hemorrhage the combination of propranolol or nadolol with isosorbid-5-mononitrate is available. Future studies will tell, whether this drug combination is superior to the nowadays established endoscopic eradication of varices, especially by long-term variceal band ligation. For primary prophylaxis of variceal hemorrhage non-selective beta-anatagonists remain the therapy of choice in compliant patients with esophageal varices and endoscopic signs indicating a high risk of bleeding. Future studies must clarify the role of the beta-antagonist-nitrate combination, as well as that of prophylactic variceal band ligation, in this setting.