The opioid epidemic is a national public health crisis. It began with the misuse of commonly used prescription opioid pain relievers and has led to the increased use of heroin and illicit fentanyl. Large-scale initiatives have begun on the federal and state level and place an emphasis on improved opioid prescribing, which have important implications for the workplace. Treatment of work injury may initiate the use of prescription opioids and result in misuse and possible overdose. Prescription drug abuse affects all aspects of society so potentially any workplace could be affected. A multifaceted approach is needed to reduce opioid morbidity and mortality and the occupational health nurse should be actively involved. The intent of this article is to provide an overview of the epidemic and its impact on health, the challenges for the workplace, and recommended strategies for the occupational health nurse to impact the problem.