PURPOSE: To standardize the indications, techniques, multimodality treatment approaches, and dosimetry to be used for yttrium-90 (Y90) microsphere hepatic brachytherapy. METHODS AND MATERIALS: Members of the Radioembolization Brachytherapy Oncology Consortium met as an independent group of experts in interventional radiology, radiation oncology, nuclear medicine, medical oncology, and surgical oncology to identify areas of consensus and controversy and to issue clinical guidelines for Y90 microsphere brachytherapy. RESULTS: A total of 14 recommendations are made with category 2A consensus. Key findings include the following. Sufficient evidence exists to support the safety and effectiveness of Y90 microsphere therapy. A meticulous angiographic technique is required to prevent complications. Resin microsphere prescribed activity is best estimated by the body surface area method. By virtue of their training, certification, and contribution to Y90 microsphere treatment programs, the disciplines of radiation oncology, nuclear medicine, and interventional radiology are all qualified to use Y90 microspheres. The panel strongly advocates the creation of a treatment registry with uniform reporting criteria. Initiation of clinical trials is essential to further define the safety and role of Y90 microspheres in the context of currently available therapies. CONCLUSIONS: Yttrium-90 microsphere therapy is a complex procedure that requires multidisciplinary management for safety and success. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies.