In the United States, from 1999 to 2019, opioid overdose, either regularly prescribed or illegally acquired, was the cause of death for nearly 500,000 people. In addition to this pronounced mortality burden that has increased gradually over time, opioid overdose has significant morbidity with severe risks and side effects. As a result, opioid misuse is a cause for concern and is considered an epidemic. This article examines the trends and consequences of the opioid epidemic presented in recent international literature, reflecting on the causes of this phenomenon and the possible strategies to address it. The detailed analysis of 33 international articles highlights numerous impacts in the social, public health, economic, and political spheres. The prescription opioid epidemic is an almost exclusively North American problem. This phenomenon should be carefully evaluated from a healthcare systems perspective, for consequential risks and harms of aggressive opioid prescription practices for pain management. Appropriate policies are required to manage opioid use and prevent abuse efficiently. Examples of proper policies vary, such as the use of validated questionnaires for the early identification of patients at risk of addiction, the effective use of regional and national prescription monitoring programs, and the proper dissemination and translation of knowledge to highlight the risks of prescription opioid abuse.