Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity, mortality and health care expenditures. Increasing evidence has demonstrated that AF is a rather late-stage clinical manifestation of the underlying pathological remodeling of the atria, i.e., atrial cardiomyopathy (AtCM). The goal of this focused review is to highlight several emerging conceptual frameworks supported by contemporary basic and clinical studies, with an emphasis on the evolving definition of AtCM, the complex atrial microenvironment, the influence of both genetic and acquired risk factors and their synergistic effects in AF pathogenesis. Finally, I stressed the importance of assessing atrial and ventricular function as a synchronized unit to better appreciate the complicated interplay between AF and ventricular dysfunction. These conceptual frameworks will help to develop better strategies for personalized and mechanism-driven AF management.