Recently, there has been a dramatic increase in the use of opioids to treat chronic noncancer pain. Opioids are also being prescribed in stronger potencies and larger doses for musculoskeletal injuries. In some cases, the use of opioids for work-related injuries may actually increase the likelihood of disability. Chronic opioid use is associated with increased risk for overdose morbidity and mortality and other nonfatal adverse outcomes. The risk of dependence and addiction is much more common than previously thought. This guideline provides recommendations for prudent opioid prescribing and addresses issues critical to the care and rehabilitation of injured workers.