In this engaging discussion, Janet Ho, Sach Kale, and Julie Childers tackle the intricate overlap of substance use disorders and serious illness. Janet shares insights on why treating these patients is so challenging, while Sach details his successful outpatient clinic for cancer patients facing addiction. They explore harm reduction strategies, such as accountability without abandonment, and debate the merits of using buprenorphine versus methadone. The trio also candidly addresses the emotional complexities clinicians face, emphasizing the need for effective communication and tailored care.