Patients with adult polycystic liver disease and massive cystic replacement of the liver may present with severe debilitation and impairment of functional performance or, rarely, with signs of portal hypertension or hepatic dysfunction. In those patients incapacitated by severe hepatomegaly secondary to massive cystic replacement with predominantly small cysts (2 cm) without areas of parenchymal sparing, liver transplantation is a therapeutic option. Five patients with incapacitating symptoms from polycystic liver disease underwent liver transplantation as a final therapeutic procedure. Two patients had previous fenestration procedures without significant relief. All patients had radiographic evidence of concomitant polycystic kidney disease; two of these patients were dialysis-dependent at the time of liver transplantation. One patient underwent combined liver-kidney transplantation, whereas another received a six-antigen matched kidney transplant 64 months after liver transplantation. Four of five patients are alive 84, 39, 20, and 8 months after successful liver transplantation. All four have returned to normal functional status with complete resolution of symptoms. Liver transplantation is a suitable option for the patient with bilobar small cystic liver disease without areas of parenchymal sparing. However, only patients with severely compromised functional status should be offered this therapy. Concomitant renal evaluation is mandatory, and a knowledge of the natural history of this disease will aid in the decision of whether a combined liver-kidney transplantation is indicated.