Portal hypertension is a hemodynamic abnormality that involves a high risk of disability as well as a reduced life expectancy in patients with cirrhosis. Progress in the knowledge of pathophysiology of portal hypertension has opened a new perspective for different pharmacological approaches. In this context, the pleiotropic actions of statins on endothelial cell function have emerged as new options to reduce portal pressure levels by targeting multiple molecular pathways involved in hepatic vascular homeostasis. We highlight how statins may target some molecular pathways involved in the pathophysiology of portal hypertension and how these drugs may correct impaired hepatic vascular tone.