The first reported operation on the upper sympathetic system was performed by Alexander in 1889. The initial indications (epilepsy, exophthalmic goiter, idiocy, glaucoma) are obsolete. For some subsequent indications (angina pectoris, vasospastic disorders, and painful conditions) sympathectomy has still a limited application. The main indications today are hyperhidrosis (since 1920) and blushing. Renewed attempts to perform the operation for psychological conditions have been reported. The technique of sympathectomy has been modified over the century, with a trend to minimize the extent of surgery: from open to endoscopic approaches; from resection of ganglia to thermoablation, thermotransection, and clipping. The sequelae of the operation (mainly compensatory hyperhidrosis) present a major problem in a small percentage of operated patients. Techniques of reversal (by nerve grafting and unclipping) have been proposed. Meticulous follow-up studies are required to evaluate the merits of these techniques. Improved knowledge of the functions and interrelations of the autonomic nervous system is required to understand the mechanism of these sequelae and learn how to avoid or treat them.