Portal hypertension is treated by reducing portal pressure in order to prevent esophageal variceal bleeding or recurrent bleeding. Because portal hypertension depends on both elevated portal tributary blood flow and intrahepatic vascular resistance, the pharmacologic therapy of this syndrome consists in reducing portal blood flow or vascular resistance, or both. The pharmacologic prevention of first bleeding or recurrent bleeding has been performed with nonselective beta-adrenergic antagonists (propranolol or nadolol). Certain controlled studies have shown that this type of drug significantly reduces the risk of first bleeding by approximately 40% in patients with esophageal varices. A meta-analysis showed that death due to bleeding was also significantly lower in the beta-blocker group than in the placebo group. Moreover, beta-blockers are effective in patients in both good and poor condition and with all types of cirrhosis. The efficacy of beta-blockers on the risk of recurrent bleeding is less clear, but these substances significantly decrease the risk of rebleeding, by approximately 30%. Recurrent bleeding in patients treated with beta-blockers is associated with the occurrence of hepatocellular carcinoma or lack of compliance. In conclusion, it is clear that different substances have portal hypotensive effects and can be used to treat or prevent complications of portal hypertension. However, other drugs should be tested, and other clinical studies are needed to identify good responders.