The global prevalence of atrial fibrillation (AF) has increased substantially over the past three decades and is currently approximately 60 million cases. Incident AF and its clinical consequences are largely the result of risk factors that can be modified by lifestyle changes. In this Review, we provide evidence that the lifetime risk of AF is modified not only by sex and race but also through the clinical risk factor and comorbidity burden of individual patients. We begin by summarizing the epidemiology of AF, focusing on non-modifiable and modifiable risk factors, as well as targets and strategies for the primary prevention of AF. Furthermore, we evaluate the role of modifiable risk factors in the secondary prevention of AF as well as the potential effects of risk factor interventions on the frequency and severity of subsequent AF episodes. We end the Review by proposing strategies that require evaluation as well as global policy changes that are needed for the prevention of incident AF and the management of recurrent episodes in patients already affected by AF.