BACKGROUND: In the past 2 decades, overdoses and deaths from prescription opioids have reached epidemic proportions in the United States. The widespread use of opioids complicates management of the orthopaedic surgery patient in the acute and chronic settings. Orthopaedic surgeons are some of the top prescribers of opioids in the complex setting of chronic use, abuse, and diversion. METHODS: The literature regarding the basic science of pharmacologic options for pain management (e.g., opioids and nonsteroidal anti-inflammatory drugs), the impact of strategies on bone and soft-tissue healing, and pain relief are summarized as they relate to the management of orthopaedic injuries and conditions. Additionally, a section on designing solutions to address the current opioid crisis is presented. RESULTS: The mechanism of action of different classes of analgesic medications is discussed, as well as the basic scientific evidence regarding the impact of narcotic and nonnarcotic analgesic medications on bone-healing and on other organ systems. Differences between pain and nociception, various treatment strategies, and clinical comparisons of the effectiveness of various analgesics compared with opioids are summarized. Finally, options for addressing the opioid crisis, including the description of a large system-wide intervention to impact prescriber behavior at the point of care using health-information solutions, are presented. CONCLUSIONS: Orthopaedic leaders, armed with information and strategies, can help lead the way to solutions to the opioid epidemic in their respective communities, institutions, and subspecialty societies. Through leadership and education, orthopaedic surgeons can help shape the solution for this critical public health issue.