Autonomic regulation therapy (ART) is a rapidly emerging therapy in the management of congestive heart failure secondary to systolic dysfunction. Modulation of the cardiac neuronal hierarchy can be achieved with bioelectronics modulation of the spinal cord, cervical vagus, baroreceptor, or renal nerve ablation. This review will discuss relevant preclinical and clinical research in ART for systolic heart failure. Understanding mechanistically what is being stimulated within the autonomic nervous system by such device-based therapy and how the system reacts to such stimuli is essential for optimizing stimulation parameters and for the future development of effective ART.