Pulmonary vascular abnormalities occurring in the setting of liver disease have been increasingly recognized as important clinical entities that influence survival and liver transplant candidacy in affected patients. The most common such abnormality, the hepatopulmonary syndrome, is found in 15% to 20% of patients with cirrhosis. These disorders have no effective medical therapies. Experimental models of hepatopulmonary syndrome have identified a sequence of hepatic and pulmonary endothelial alterations that lead to nitric oxide and carbon monoxide-mediated intrapulmonary vasodilatation. A key role for shear stress-mediated pulmonary endothelial endothelin B receptor overexpression and cholangiocyte ET-1 production and release has emerged as a mechanism for local nitric oxide production in the lung. How these alterations are influenced by bacterial translocation and the systemic hyperdynamic circulatory state and whether similar changes occur in human disease are areas of ongoing investigation.