Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumour, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs, however this ambition remains to be realised. In view of this lack of progress, the FDA-AACR-ASTRO Clinical Development of Drug-Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups and the FDA in order to discuss challenges to introducing new drug-radiotherapy combinations to the clinic. This "Perspectives in Regulatory Science and Policy" article summarises the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies which efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation and patient-reported outcomes. Novel approaches including immune-oncology or DNA repair inhibitor agents combined with radiotherapy should be prioritised. In this article, we focus on how the regulatory challenges associated with defining a new drug-radiotherapy combination can be overcome in order to improve clinical outcomes for patients with cancer.