Substance misuse among medical trainees is a serious ongoing concern. The goal of this review is to describe the contributing factors leading to substance misuse among medical trainees, the consequences for those with substance misuse issues, and explore potential interventions and policy changes to address the issue. There are demographic characteristics that contribute to a higher likelihood of substance misuse including race, sex, relationship status, and year of training. Loss of training position, legal consequences, medical errors, and premature death are some of the negative effects more likely for those with substance use issues. There is a lack of clarity regarding institutional substance use policies and implementation of standardized, evidence-based policies is limited. There are many barriers preventing those with substance use issues from seeking care. Educational sessions targeted at recognizing signs of substance misuse and identification of resources have shown efficacy, while spiritual health support may be an effective area of intervention. There are many factors perpetuating substance misuse among this population. Strategies to address this issue should target improving the utilization of resources, updating institutional policies, and supporting spiritual health.