Hepatorenal syndrome (HRS) type I is a unique form of acute kidney injury resulting from renal vasoconstriction in the setting of systemic and splanchnic arterial vasodilation in patients with end-stage liver disease. The only definitive treatment currently available is liver or liver-kidney transplantation. The goal of extracorporeal support (ECS) systems in HRS is to bridge eligible liver failure patients to transplantation or functional recovery by means of detoxification, assistance with biosynthesis of key metabolic products, and regulation of inflammation. ECS systems in liver disease can be divided into two broad categories: cell-based and noncell-based systems. While cell-based systems aim to provide functions similar to those of normal hepatocytes, noncell-based systems do not incorporate tissue; they provide detoxification utilizing membranes and adsorbents. There are no standard guidelines for the application of ECS systems. Published studies are too small and show considerable differences in primary indication, primary endpoint, and treatment protocols for "intervention" and "standard" treatment groups. This article reviews the available evidence regarding the optimal use of ECS devices in HRS, makes evidence-based practice recommendations, and delineates key questions for future studies. © 2011 Wiley Periodicals, Inc..