Gastroesophageal varices are a direct consequence of portal hypertension. Nonselective beta-adrenergic blockers decrease portal pressure and are effective in preventing variceal hemorrhage. However, a large multicenter placebo-controlled trial demonstrates that nonselective beta-adrenergic blockers are not effective in preventing the development of varices and are associated with a significant rate of adverse events. This therapy is, therefore, not recommended in compensated cirrhotic patients without varices at large. In this very compensated group of patients with cirrhosis (stage 1, ie, without varices and without ascites or encephalopathy) the predictive value (both for the development of varices and for the development of clinical decompensation) of a baseline hepatic venous pressure gradient greater than 10 mm Hg is confirmed, supporting this threshold level as one that defines a clinically significant portal hypertension. Importantly, reductions in hepatic venous pressure gradient >10% are associated with a significant reduction in the development of varices, a therapeutic goal that could be achieved through the use of beta-blockers or other drugs being developed for the treatment of portal hypertension.