The rate of annual drug overdose deaths in the USA recently topped 100,000 (CDC/National Center for Health Statistics 2021), an illustration of the critical need to prevent and treat substance use disorders (SUDs). As a complex, chronic medical condition, substance use treatment requires psychological, emotional, and spiritual interventions along with medical care. The recently developed concept of moral injury has been increasingly studied and applied to military service members who experience conflict between the expectations or survival needs of combat and their moral values. This review explores whether moral injury, along with the related emotional, psychological, and spiritual symptoms, can also develop in the context of SUDs. This review identified 5 manuscripts related to moral injury arising in a substance use context. These studies were small in sample size and qualitative in nature but did indicate the presence of moral injury within the context of substance use. Further studies are needed to better understand and treat moral injury related to SUDs. A conceptualization of how moral injury may arise in the context of substance use is presented here. It is suggested that the activation of the primitive dopaminergic reward system causes a potential conflict between the experienced need for the addictive substance and a person's moral code or values. The moral injury resulting from this collision may impact treatment and recovery.