Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that may induce severe hypoxemia. Microvascular dilation and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced echocardiography, perfusion lung scanning, and pulmonary arteriography are three currently used diagnostic imaging modalities that identify the presence of intrapulmonary vascular abnormalities. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation. No medical therapy is established as effective for HPS. At the present time, liver transplantation is the only available treatment for HPS.