Intra-arterial radioembolization using microspheres labeled with the high-energy beta-emitter yttrium-90 ( 90 Y) is an innovative therapeutic strategy for primary and secondary hepatic malignancies. An accurate imaging workup plays a pivotal role in correctly selecting patients for treatment, to avoid severe complications and in assessment of the post-administration microsphere distribution. Nuclear medicine imaging modalities are an integral part of a complex multidisciplinary approach. In particular, hepatic perfusion imaging with 99m Tc-macroaggregated albumin particles ( 99m Tc-MAA), which identifies extrahepatic accumulation of radiopharmaceutical and lung shunt, is necessary to correctly select patients who may benefit from the treatment. Furthermore, 99m Tc MAA SPECT-based dose planning may optimize RE efficacy, overcoming the limitations of empirical methods to determine the activity to be administered. Quantitative assessment of the post-administration intrahepatic microsphere distribution with SPECT or PET is important for evaluation of toxicity and efficacy and can be used for the prediction of patient response and for patient-specific therapeutic dose optimization. Finally, [ 18 F]FDG PET/CT imaging is important in the assessment of early response after RE and in predicting patient outcome. This review provides a comprehensive overview of multimodality imaging in the complex management of patients undergoing RE for liver tumors.