Substance use disorders (SUDs) are a major leading cause of disability in the United States. Emerging literature suggests that patients with cancer are not immune from the burden of SUDs; substance use rates range from 2% to 35% across the cancer continuum. Substance use may predate cancer or develop during and after cancer treatment commonly in the context of pain and symptom burden management. In the setting of cancer, substance use presents a complex set of challenges for both the patient and the treatment team. Ongoing substance use reduces treatment compliance, is associated with worse health-related quality of life, complicates cancer treatment, and obstructs pain and symptom management. Unfortunately, many psycho-oncology practitioners lack knowledge about SUDs. To address this gap, this chapter broadly discusses the epidemiology, identification, and clinical management of substance use disorders within the context of cancer populations. It provides recommendations for the evaluation and treatment of cancer patients with a history of SUDs.