Ever since atrial fibrillation (AF) was first recognized in young people (so called “lone” AF) over 4 decades ago, there has been increasing focus on determining the underlying pathophysiology of condition. Although lone AF is presumed to be a highly heterogeneous disease, recent studies have identified novel risk factors such as inflammation, oxidative stress, endurance sports and genetics, for the arrhythmia. This monograph aims to highlight some of the recent advances in our understanding of the molecular pathophysiology of lone AF especially insight provided by contemporary genetic studies. These insights may provide novel therapeutic targets for treatment of this challenging arrhythmia in young patients.