Purpose: High-dose-rate (HDR) brachytherapy plays a potential curative role in the treatment of prostate cancer. An expert panel was convened to review the recent literature and reach a consensus on its appropriate clinical applications. Methods and Materials: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results: A summary of HDR brachytherapy's clinical applications and recent literature review was completed. Three clinical variants were developed to address common HDR dose, fractionations, and indications for its use in definitive therapy for primary and local recurrent prostate cancer. The panel reached a consensus on the specific treatment approaches with numerical rating and commentary. Conclusions: In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate application of HDR brachytherapy for prostate cancer. © 2014 American College of Radiology.