At present, the systemic treatment of unresectable colorectal cancer liver metastases involves oxaliplatin and irinotecan-based chemotherapy regimens combined with targeted therapies such as bevacizumab (Avastin) and cetuximab (Erbitux). Radiation therapy, traditionally, is not considered a viable treatment modality owing to its unacceptably high hepatic toxicity, and still steering traditional wisdom or dogma that chemoradiation cannot be an oncological strategy for a stage IV disease. Selective internal radiation treatment with yttrium-90 (Y-90) radiomicrospheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio. Since its early clinical trials, it has demonstrated improved response rates when used in conjunction with systemic or regional chemotherapy. This article reviews the clinical role for Y-90 radiomicrosphere therapy in the contemporary management of colorectal cancer liver metastases. All the structured clinical trials, to date, are summarized, including those that studied the value of combined Y-90 radiomicrosphere therapy and current chemotherapy protocols.