Dr Brittany B. Dennis, Dr Catherine Anne Lovatt, and Dr Elahn Pogue—internal medicine residents at McMaster University—review current evidence for opioid substitution therapies, highlight methodologic limitations and the implications for risk mitigation and treatment for opioid use disorder (OUD), summarize important risk factors affecting treatment outcomes (evidence from the McMaster's GENOA study), and describe clinical and demographic trends observed in high-risk patients admitted to hospital with OUD. The webinar chaired by Dr Mohamed Panju was recorded at the Chair's Medical Grand Rounds on December 16, 2021.