Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351Funder: Royal Society through a University Research Fellowship and the Engineering and Physical Sciences Research Council (EPRSC)Funder: China Scholarship Council (CSC); doi: https://doi.org/10.13039/501100004543Abstract: Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies