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Heart failure (HF) is associated with significant morbidity and mortality and an increasing economic burden. The persistence of HF’s risk factors, coupled with an aging population, also leads to an increase in its incidence and prevalence. It is well established that sympathetic hyperactivity and parasympathetic withdrawal are instrumental in the development and worsening of HF. Therefore, restoring autonomic balance to the cardiovascular system is an attractive therapeutic approach. The following is a review of current clinical trials of device-based autonomic regulation therapy in the management of HF with a reduced ejection fraction.