Background: Hydromorphone, a potent analogue of morphine, has long had an important role in pain management and is included in several international guidelines for managing pain. Advances in hydromorphone formulations and the ways in which hydromorphone is being used clinically today warrant a review of the drug's pharmacotherapeutic utility. Objective: The history and recent advances in hydromorphone pharmacotherapy are reviewed. Areas covered include the pharmacologic and metabolic profile of hydromorphone, the role of hydromorphone in pain management, formulations and routes of administration, and issues related to relative opioid potencies, equianalgesic ratios, and opioid rotation. Because hydromorphone, like all opioids, carries a risk of misuse, abuse, and illicit diversion, the related issues of tamper-resistant formulations and "dose-dumping" of extended-release formulations are discussed. Conclusions: Due to the epidemic of prescription opioid overdoses associated with prescription opioid abuse in the United States, development of tamper-resistant opioid formulations that avoid dose-dumping issues has become a significant goal of pharmaceutical manufacturers. The current formulation of hydromorphone extended-release potentially provides the benefits of long-acting hydromorphone (ie, continuous pain control, increased quality of life, freedom to perform daily activities) to appropriate patients, while reducing the risks of abuse and without compromising safety. (C) 2013 Elsevier HS Journals, Inc. All rights reserved.