Research into cardiac autonomic control has received great interest in the past 20 years, and we are now at a critical juncture with regard to the clinical translation of the experimental findings. A rush to develop clinical interventions and implant a range of devices aimed at cardiac neuromodulation therapy has occurred. This interest has been driven by research, superimposed on commercial opportunities and perhaps the more relaxed regulatory framework governing implantable devices and interventions compared with that for pharmacotherapy. However, many of the results of the clinical trials into these therapies have been disappointing or conflicting. This lack of positive results is partly attributable to a scramble to find simple solutions for complex problems that we do not yet fully understand. Are there reasons to be optimistic? In this Review, we highlight areas in the field of cardiac autonomic control that we feel show the most promise for clinical translation and areas in which our current range of blunt tools need to be refined to bring about long-term success in treating arrhythmias.