Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression. In this Review, we identify the causes of medication non-adherence and summarize interventions that have been proven in randomized clinical trials to be effective in improving adherence. Practical solutions and areas for future research are also proposed.