Clinical decisions regarding the treatment of metastatic colorectal cancer require consideration of current and evolving modalities to best achieve prolonged patient survival. Clinical trials have established that for first-line treatment of patients with or without extrahepatic metastases, radioembolization augments the response produced by chemotherapy in patients with unresectable liver metastases. This includes progression-free and overall survivals that compare favorably with phase II to III data of current chemotherapy regimens. The increased response rate with radioembolization and first-line chemotherapy may improve the likelihood for potentially curative hepatic lesion resection or ablation. Application of an innovative multidisciplinary treatment approach that integrates radioembolization and local ablative therapy may enable the benefits of curative hepatic resection to be extended to a broader group of patients.