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Heart failure (HF) is associated with significant morbidity and mortality. The disease is characterised by autonomic imbalance with increased sympathetic activity and withdrawal of parasympathetic activity. Despite the use of medical therapies that target, in part, the neurohormonal axis, rates of HF progression, morbidity and mortality remain high. Emerging therapies centred on neuromodulation of autonomic control of the heart provide an alternative device-based approach to restoring sympathovagal balance. Preclinical studies have proven favourable, while clinical trials have had mixed results. This article highlights the importance of understanding structural/functional organisation of the cardiac nervous system as mechanistic-based neuromodulation therapies evolve.