The role of traditional whole liver irradiation in the treatment of unresectable intrahepatic cancers has been limited by low liver tolerance. The development of three-dimensional (3D) conformal radiation treatment planning offers the potential to treat tumor-bearing portions of the liver to a far higher dose than the entire liver could tolerate, while sparing uninvolved liver. This concept resembles that used by the surgeon, who determines resectability based on the function of the liver anticipated to remain after resection. We have treated patients with unresectable intrahepatic cancers by combining 3D conformal irradiation with intraarterial hepatic floxuridine, which our laboratory studies show is a radiation sensitizer. We have delivered more than 70 Gy to parts of the liver without producing significant radiation hepatitis. Furthermore, the median survivals of patients with primary hepatobiliary cancer (19 months) and colorectal cancer metastatic to the liver (22 months) approach those achieved by surgical excision in a more favorable group of patients.