One hundred years have elapsed since Thomas Jonnesco performed the first left cardiac sympathetic denervation (LCSD) in a patient with unmanageable angina pectoris and ventricular tachyarrhythmias, and the progress in the field has surpassed imagination. Here we will review the historic basis of cardiac sympathectomy for the management of life-threatening arrhythmias and will then discuss the often forgotten critical experimental studies that provided the rationale for the amazing growth of its role in clinical management. We will then mention the evolution in the surgical approaches, with their pros and cons. Similarly, we will address the existence of different views on the wisdom of starting with unilateral LCSD versus performing at outset bilateral CSD. The main results in the two diseases for which LCSD has already a definite role (namely the long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) will be reviewed and discussed, touching also on the medico-legal implications descending from the clear efficacy of LCSD for these conditions. Finally, we will consider the potential value of LCSD for other clinical conditions and will close by mentioning a new randomized clinical trial in which LCSD is performed in patients with heart failure.