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Radioembolization aims to selectively target radiation to all liver tumors while limiting the dose to normal liver parenchyma. The deposition of yttrium-90 (90Y) microspheres delivered through the hepatic artery are preferentially implanted within liver tumors in a 3:1 to 20:1 ratio compared with a normal liver. The principles and mode of action of radioembolization are fundamentally different from the conventional embolization of liver tumors through transarterial embolization or chemoembolization. A meticulous work-up, involving computed tomography scanning, contrast-enhanced magnetic resonance imaging, and transfemoral hepatic angiogram, is essential to assess the appropriateness of the patient for treatment. A simulation of the treatment, done with technetium-99m-labeled macroaggregated albumin particles, which approximate the size of microspheres, is used to identify the shunting of microparticles to the lungs or gastrointestinal tract, thus helping to determine patient selection. Whole-liver or unilobar treatment approaches are chosen according to the anatomic distribution of the tumors, concomitant factors affecting liver function, and institutional preferences. Optimal periprocedural care, discharge planning, and follow-up care are essential to assess treatment response and ensure that short-term side effects of radioembolization are adequately managed. The expanding literature on radioembolization shows that this is an effective treatment for the management of both primary and metastatic tumors.