Among the many people experiencing grief in response to opioid overdose deaths, individuals with opioid use disorder (OUD) bear one of the largest emotional burdens. Grief and loss of social support networks have the potential to destabilize OUD and result in overdose, suicide, and other harmful consequences. However, few clinicians discuss how overdose losses impact their patients with OUD, let alone consider the role of grief in treatment outcomes. Lessons from the acquired immunodeficiency syndrome (AIDS) epidemic and crack cocaine crisis can inform our understanding of grief in the context of stigma and societal injustices. In this commentary, we describe how these historical lessons can be adapted to the opioid overdose crisis to improve the care of people with OUD.