The phenomenon of lateral sprouting of axons into an end-to-side sutured recipient nerve is well documented. The exact nature, however, still needs further investigation. Since 1996, we have been continuously involved in primate research as well as using this end-to-side nerve suture (ETSNS) method in clinical practice. Fifty-six patients with a variety of conditions, ranging from brachial plexus avulsion to digital nerve lesions, have been operated. From our experience, it seems that the best results achieved are proximal motor re-innervation (e.g. biceps) and distal sensory re-innervation (e.g. volar skin of the hand). The discussion will cover various aspects for ETSNS in the human patient, such as indications, parameters, technique, and the importance of rehabilitation. ETSNS restores function in conditions previously difficult to operate, and may replace nerve grafting in many instances. It provides an additional method in our armamentarium in peripheral nerve surgery.