The accumulating literature linking stress with negative health outcomes, including cardiovascular disease (CVD), is extensively reported yet poorly defined. Stress is associated with a higher risk of hypertension, acute myocardial infarction, arrhythmogenesis, and heart failure. Stress mediates its effect through direct neuronal, endocrine, autonomic, and immune processes and indirectly by modifying lifestyle behaviors that promote CVD progression. Stress occurs when an individual perceives that internal or external demands exceed the capacity for an adaptive response. Psychologic stress is increasingly recognized in the atrial fibrillation (AF) population, although the pathophysiology remains unclear. There appears to be a bidirectional relationship between AF and stress with a complex interplay between the 2 entities. Stress modulates the immune and autonomic nervous systems, key drivers in AF initiation and potentiation. AF leads to increasing anxiety, psychologic distress, and suicidal ideation. Recently, lifestyle modification has emerged as the fourth pillar of AF management, with stress reduction a potential reversible risk factor and future target for intervention. This review examines proposed mechanisms linking AF and stress and explores stress reduction as an adjunct to the AF management armamentarium.