Atrial fibrillation (AF) is the most common arrhythmia in adults and contributes directly to adverse clinical events, ranging from ischemic stroke to heart failure and cardiovascular death. Because the incidence of AF and its attendant complications increase with age, there is a strong and growing need to develop safe, effective and widely available therapies. The following review summarizes the use of oral anticoagulants in older adults with AF, focusing on practical topics such as drug metabolism, drug-drug interactions, co-morbidities and cost considerations in a complex payer environment.