Sympathoactivation is a prominent feature of heart failure (HF). Its role in cardiac remodeling and arrhythmogenesis is well-recognized today, although incomplete understanding of autonomic mechanisms was a barrier to development of contemporary medical therapies. Despite widespread availability of drugs and devices, mortality and morbidity in HF remain unacceptably high. Recognition of an additional phenotype, HF with preserved ejection fraction (EF), poses additional challenges. New treatment options are required. Electrical modulation of the central nervous system with baroreflex activation therapy offers a new approach. Activation of this afferent pathway induces the central nervous system to rebalance autonomic modulation of the cardiovascular system. Results in animal models of HF demonstrating increased survival and beneficial cardiac remodeling recently led to a clinical feasibility study in HF with reduced EF wherein the clinical course of patients dramatically improved. Results in resistant hypertension patients further suggest potential for benefit in HF with preserved EF.