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This article summarizes the literature on current definition, suggested pathogenetic mechanisms and the role of laboratory assessment in the differential diagnosis of hepatorenal syndrome (HRS) from other causes of renal disease that may arise during hepatic cirrhosis and some diseases affecting both liver and kidney. It should be remembered that the main theory suggested for the pathogenesis of HRS is the arterial vasodilation hypothesis of portal hypertension, ending in type 1 and type 2 HRS, but there is no consensus supporting either mechanism as a solid theory for initiation of HRS pathogenesis to date. No laboratory test can firmly establish a diagnosis of HRS, which is mainly based on the absence of any specific cause of renal failure. Laboratory and ultrasonographic tests based on non-invasive techniques are being investigated as possible diagnostic approaches.