Background: Hepatopulmonary syndrome (HPS) is an important complication of liver cirrhosis. It is due to vasodilation and angiogenesis in the pulmonary vascular bed, which lead to ventilation-perfusion mismatching, diffusion limitation to oxygen exchange, and arteriovenous shunting. Pulmonary vasodilation in experimental HPS is mediated by a number of endogenous vasoactive molecules, including endothelin-1 (ET-1) and nitric oxide (NO). Liver injury stimulates release of ET-1, which increases expression of ETB receptors in pulmonary endothelial cells. Activation of these receptors results in the upregulation of endothelial NO synthesis (eNOS) and subsequent increased production of NO, which diffuses into vascular smooth muscle, causing vasodilation. In addition, increased phagocytosis of bacterial endotoxin in the lung promotes activation of inducible NO synthase (iNOS), which also contributes toward increased NO production. Bacterial translocation and subsequent monocyte accumulation may also stimulate pulmonary angiogenesis in HPS, which may be partly controlled by genetic factors. Conclusion: However, there remains a need for more human experimental data to support the development of new therapies targeting these proposed mechanisms. Despite promising outcomes from treatment of HPS with several drugs, results can not be generalized to all patients due to the lack of randomized trials. Promising drugs are considered Pentoxifylline, Methylene blue and Mycophenolate mofetil. Currently the most effective treatment is liver transplantation.