Intra-arterial radionuclide therapies serve essentially as internal radiation treatment options for both primary and metastatic liver tumors, which imply delivering implantable radioactive microspheres into branches of hepatic arteries that feed liver tumors to provide a high dose of targeted radiation to tumor tissue, while sparing the healthy liver tissue from hazardous effects of radiation. The principle of this therapeutic option depends on the unique preferential arterial supply of malignant liver tumors in contrast with mostly portal venous supply of normal hepatocytes as well as excess amount of arterial neovascularization in the tumor bed. Therefore, intra-arterial radionuclide therapy can provide very high radiation exposure to tumor tissue, which is impossible to reach with external radiation therapy due to serious side effects and moreover, radiation can be targeted to tumor tissue selectively with less side effects. Yttrium-90 (Y-90), a high-energetic beta emitter is the most preferred radionuclide, which is used to label microspheres. Two types of Y-90 microspheres are commercially available that are made of resin and glass. Many studies in the literature have demonstrated that Y-90 microsphere therapy is an efficient and safe locoregional therapeutic option for unresectable primary and metastatic liver tumors such as hepatocellular carcinoma and liver metastases from colorectal cancer and breast cancer as well as neuroendocrine tumors. Furthermore, limited number of studies has reported its use in some relatively uncommon metastatic liver tumors from melanoma, pancreatic, renal, and lung cancer. Besides Y-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, Rhenium-188 microspheres, Holmium-166 chitosan, and Holmium-166 microspheres have been introduced as alternative radiopharmaceuticals for intra-arterial therapy for liver tumors. (C) 2016 Elsevier Inc. All rights reserved.