There are many areas of uncertainty surround immunotherapy, which require further exploration in the coming years. Speaking from the British Thoracic Oncology Group (BTOG) Annual Conference 2018, held in Dublin, Ireland, Fred Hirsch, MD, PhD, of University of Colorado, Denver, CO, discusses some of the most pertinent issues, including resistance mechanisms and the sequencing of therapies. Prof. Hirsch also highlights the need for the further study of immunotherapy in the locoregional and localized settings.