The United States is in the midst of an opioid use epidemic, which has severe medical, social, and economic consequences. Addictions to and abuse of prescription and illicit opioids are increasing, and emergency department radiologists are increasingly being faced with the task of examining patients who present with opioid-related complications. These complications may be the result of direct drug toxicity or nonsterile injection of the drugs. Neurologic, musculoskeletal, cardiopulmonary, genitourinary, and gastrointestinal complications may be evident at diagnostic imaging in emergent settings. Heroin-induced leukoencephalopathy, cerebral septic emboli, mycotic arterial aneurysms, soft-tissue infections, and infective endocarditis are some of the conditions that patients may be found to have after they present to the emergency department. In this article, the above topics, including clinical features, pathophysiology, imaging findings, and treatment options, are reviewed. Recognizing the limitations of diagnostic imaging modalities that are available to radiologists is equally important, as some conditions can be successfully diagnosed after the initial triage-for example, transesophageal echocardiography can be performed to diagnose infective endocarditis. The emergency department radiologist may be responsible for identifying acute conditions, which can be life threatening. Some of the more common emergent opioid-related conditions and complications are reviewed, with specific emphasis on cases in which emergency department radiologists encounter conditions for which additional expertise is required. Becoming familiar with the conditions directly related to the current opioid epidemic will enable the diagnosis of these entities in a timely and accurate manner. ©RSNA, 2018.