Radioembolization is a proven treatment to slow disease progression and improve survival in patients with colorectal cancer liver metastases and hepatocellular carcinoma. Accumulating evidence supports its use in metastases from neuroendocrine tumors and breast cancer. Cancers with radiobiologic profiles similar to those of colorectal and breast cancer, including melanoma, lung cancer, and nodular cholangiocarcinoma, are being studied as candidates for radioembolization. This treatment modality has also been shown to downsize hepatic tumors for potentially curative ablation in patients with breast, pancreatic, and colorectal cancer. Radioembolization using either yttrium-90 ((90)Y)-labeled resin or glass microspheres represents a promising therapy for liver-only or liver-predominant tumors in patients with 1 or more variables, including adequate or sufficient functional liver reserve, good performance status, and absence of other significant comorbidities. Therapeutic efficacy and safety can be best achieved by use of careful dosimetric techniques and treatment planning. Radioembolization could be considered after progression of liver metastases during treatment hiatus, at an early therapeutic line in tumors that respond poorly to chemotherapy, or in treatment-refractory disease.