Systemic hypertension is the most consistent modifiable risk factor for atrial fibrillation (AF) in adults with consistent data from both animal models and human studies suggesting a consistent pattern of autonomic imbalance underlying both conditions. Relative sympathetic nervous system activation is a demonstrably common attendant to the local mechanisms in pulmonary veins that sustain persistent or recurrent AF and may represent a new objective for adjunctive treatment. Established management of AF aims to achieve durable control through either pharmacologic or catheter-based interventions. The introduction of catheter-based renal denervation as a safe, alternate approach to target the sympathetic nervous system therapeutically represents a potential opportunity to treat the shared pathophysiological mechanisms with minimal additional treatment burden when added in this context. Preliminary investigations have demonstrated both proof-of-concept and the technical feasibility of combined renal denervation and AF ablation procedures with the suggestion of benefit in terms of freedom from AF recurrence. The available data is promising but absolute confirmation of efficacy remains unconfirmed in the absence of more definitive evidence. This paper reviews the role of autonomic imbalance in the initiation and maintenance of AF by summarizing the observations from both experimental models and clinical studies from the perspective of potential therapeutic overlap between catheter-based treatments.