Heart failure with reduced ejection fraction (HFrEF) is a common, incompletely treatable, complex, progressive, and severe medical problem despite guideline-directed medical therapy. HFrEF is associated with sympathetic activation and parasympathetic inhibition; these reflexive processes may ultimately be maladaptive and exacerbate or even perpetuate the problem. Attempts to regulate, autonomic tone during HFrEF in animal models and in humans has shown promise with beneficial effects that include improvement in symptoms, mitigation of arrhythmic events, reduction in mortality, and correction in hemodynamics. Several modalities to regulate autonomic tone such as unilateral parasympathetic nerve activation, baroreceptor activation, renal nerve ablation and spinal cord stimulation have been investigated. Although they demonstrated some benefit, the long-term efficacy in HFrEF has not been proven. Considering specific limitations of each modalities, to draw definitive conclusions is impossible at this time. Here, we review the present state-of-the-art of device of autonomic regulation therapy to affect outcomes in HFrEF