Acute kidney injury (AKI) secondary to hepatorenal syndrome (HRS) is an ominous complication of end-stage liver disease (ESLD). In HRS, splanchnic and peripheral vasodilatation with reduction in effective arterial volume causes activation of mechanisms leading to intense renal vasoconstriction and functional AKI. HRS is a diagnosis of exclusion and all other causes of AKI (especially prerenal azotemia) have to be considered and excluded. Spontaneous bacterial peritonitis (SBP) frequently precipitates HRS and should be ruled out in all ESLD patients presenting with AKI. Prompt therapy of SBP with intravenous antibiotics and albumin lessens the risk of developing HRS. Combined use of intravenous albumin, splanchnic and/or peripheral vasoconstrictors, and renal replacement therapy (RRT) are only bridges to early liver transplantation (or combined liver-kidney transplantation in selected patients). Transplantation is the only definitive way of improving the long-term prognosis. Close collaboration between hospitalists/internists managing HRS patients and hepatology and nephrology consultants is critically important.