Autonomic nervous system (ANS) has a crucial role of regulating cardiac function in the physiological state and contributes to the pathogenesis of arrhythmias in the diseased state. The cardiac neuraxis consists of multiple feedback loops consisting of efferent and afferent limbs, mediating neurotransmission to and from the heart. Efferent parasympathetic neurotransmission is mediated by the vagus nerve, while paravertebral sympathetic ganglia relay efferent sympathetic neurotransmission to the heart. The association between autonomic activity and ventricular arrhythmias (VAs) has been studied extensively in both experimental models and humans. Efferent parasympathetic activity is felt to be antiarrhythmic, while the activation of efferent sympathetic signals is proarrhythmic. The cardiac neuraxis undergoes remodeling and becomes dysfunctional in the setting of myocardial infarction (MI), chronic cardiomyopathy (CMY), and structural heat disease. Altered ANS function has been shown to initiate and/or maintain VAs via various mechanisms. Interventions targeting the ANS have been used clinically to treat VAs, particularly in patients with hereditary heart rhythm disorders and structurally abnormal hearts. Clinical applications of cardiac neuraxial modulation at the level of spinal cord, stellate ganglion, and peripheral sympathetic and vagus nerve are being developed. In this review, the anatomy of cardiac autonomic innervation, the association between autonomic activity and ventricular arrhythmogenesis, and clinical applications of neuraxial modulation in the treatment of VAs are discussed.