Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Importance: Heavy menstrual bleeding (HMB) is a common complaint among reproductive-aged women, which negatively affects their health as well as their social, professional, and family lives. Modern medical management usually provides effective control of HMB irrespective of the underlying cause. Surgical interventions should be reserved for women with significant pelvic pathology and those unresponsive to medical therapy. Objective: The aim of this review was to provide a comprehensive summary of the efficacy and safety of available medical treatments of HMB. Evidence Acquisition: A comprehensive MEDLINE and EMBASE literature search was undertaken using selected terms associated with HMB to identify clinical studies published before March 20, 2013, that reported changes in menstrual blood loss in women receiving medical intervention. Results: The effectiveness of treatments to reduce HMB due to endometrial dysfunction in descending order was as follows: (1) the levonorgestrel-releasing intrauterine system (LNG-IUS) (initial release rate of 20 g of LNG per 24 hours), (2) combined hormonal contraceptives (oral or transvaginal), (3) tranexamic acid, and (4) longcourse oral progestogens (.3 weeks per cycle). The LNG-IUS was found to reduce HMB due to some structural causes (leiomyomas and adenomyosis). The reduction in menstrual blood loss achieved with nonsteroidal antiinflammatory drugs and short-course oral progestogens (.14 days per cycle) is less impressive but may be sufficient for women who have marginally increased blood loss. Conclusions and Relevance: For women not seeking pregnancy, the LNG-IUS is the first-line medical therapy for HMB, with combined hormonal contraceptives as second choice. For other women, fewer effective options exist.