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Chronic diseases – conditions that require ongoing medical treatment, and last a year or more – are estimated to make up roughly three quarters of the global disease burden. Further, their prevalence is on the rise, in part due to our ageing population. Improvements in prevention, detection, and treatment are crucial in order to combat this massive and growing problem. This Collection highlights new research on the incidence, risk factors, underlying causes, diagnosis, and potential therapies for some of the most common and most intractable chronic conditions.