A critical component of the liver transplant (LT) evaluation process is the identification of co-morbid medical or psychiatric conditions that might adversely impact LT outcomes. The ingestion of substances, both legal and illicit, is a leading cause of preventable death worldwide and, by extension, can adversely impact both graft and recipient survival after LT. Harmful alcohol consumption is a leading cause of morbidity and mortality worldwide. Harmful alcohol consumption has a negative effect on post-LT outcomes as well, regardless of the primary indication for LT. Cigarette smoking is associated with significant morbidity and mortality after LT. Tobacco use is listed in American and European guidelines as an absolute contraindication to transplant, although many centers disregard this advice. Cannabis/Marijuana use, and possible cannabis use disorder, should be considered as part of the broader psychosocial LT candidate assessment.