For the past three years, our attention has been focused on the health of our patients, staff and families and on reopening our practices in the COVID-19 pandemic. Despite encouraging signs of improvement, the Opioid epidemic continues to claim lives at an increasing rate. The current status of this crisis will be defined at the national and state levels. The various types of orofacial pain and the appropriate treatment strategies for each diagnosis will be discussed together with a comparison of the use of opioids, non-opioid medications, and non-pharmacologic options for safe and effective pain management. Best practice guidelines for pain control after different types of dental procedures will be evaluated. The risks, benefits, alternatives, storage, and disposal of controlled substances will be detailed. Simple means of identifying and managing patients at risk for substance misuse will be described. Regulatory and legal requirements will be documented. Resources for the safe use of opioids will be provided.