Atrial fibrillation (AF) is a common arrhythmia with a tremendous impact on quality of life and mortality. Its prevalence continues to rise alongside the increasing obesity and type 2 diabetes epidemics, raising a need for improved therapeutic strategies and a better understanding of the factors and mechanisms that drive metabolic disease-associated AF. To this end, the link between AF and metabolic disease is being increasingly explored in observational, clinical, and experimental studies. Chronic inflammation is a hallmark of metabolic disease, and multiple studies have also demonstrated a strong relationship between AF and inflammation. In this review, we discuss recent advances in our understanding of the mechanisms governing the development of AF in the context of metabolism and inflammation, related concepts in therapeutic development, and a novel role for calcitonin in AF.