Systemic therapy for cancer is evolving rapidly, with drugs that promote anti-tumour immunity becoming ever more present in the clinic. Immunotherapy is now standard therapy for several cancers including melanoma, lung cancer, renal cell cancer, head and neck cancer, urothelial cancer, and Hodgkin’s lymphoma. It is anticipated that most patients will be treated with immunotherapy in the near future. Clinical trials have routinely excluded patients with pre-existing autoimmune disease, organ transplants, poor performance status, chronic viral infections, and those at extremes of age, and yet these patients are often in out clinics. This presentation will discuss what is known, and what is unknown, regarding the safety and efficacy of immunotherapy in non-trial populations.