Certain vasoactive substances reduce portal pressure in patients or animals with portal hypertension by either inducing splanchnic vasoconstriction or reducing hepatic vascular resistance. Studies have shown that propranolol or nadolol significantly reduce the risk of a first episode of gastrointestinal (GI) bleeding and increase the survival rate in patients with cirrhosis and oesophageal varices. Isosorbide-5-mononitrate is also effective in the prevention of bleeding. The combination of beta-blockers and nitrates may be more effective than one drug alone. These results show that beta-adrenoceptor antagonists must be used to prevent the first episode of GI bleeding. Beta-blocker administration also significantly reduces the risk of recurrent GI bleeding and increases the survival rate in patients with cirrhosis. Studies have shown that propranolol is as effective as endoscopic sclerotherapy. The combination of a beta-blocker with endoscopic sclerotherapy may be more effective than pharmacological or endoscopic treatment alone for the prevention of rebleeding. Finally, new experimental and clinical studies are needed to improve the pharmacological treatment of portal hypertension.