Embolotherapy with radioactive microspheres, radioembolization, is gaining clinical acceptance as a therapeutic option for patients with liver malignancies. Knowledge of the anatomic variants in the mesenteric system is critical to safely administer this therapy. The purpose of this review is to provide a thorough discussion and detailed presentation of the technical aspects of radioembolization specifically as it pertains to the implantation devices. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. In addition, the basic principles described in this manuscript apply to all liver-directed transarterial therapies, such as chemoembolization and/or drug-eluting microspheres.