Peripheral nerve lesions represent debilitating conditions that determine sensitive, motor and associated psychosocial losses, deeply and severely affecting the quality of life. Despite adequate microsurgical repair, functional results are variable and often dissatisfying. This study aimed to analyse and discuss peripheral nerve lesion cases from our clinic, involving the upper limb, an anatomical segment with impactful functional importance. We followed the distribution of nerve lesions throughout a three-year period, describing the patients’ characteristics and the therapeutic protocols. Furthermore, we reviewed the relevant literature to identify potential therapeutic strategies that may help optimize functional results. In the presented clinical study, most of the patients benefited from direct microsurgical repair of the nerve injury. However, we had a series of cases of nerve defects that could not be approached with primary repair. When a nerve cannot be repaired by direct neurorrhaphy, there are different options for bridging the nerve gap, each with its indications and advantages. Autografts still represent the gold standard in treating nerve gaps, but other procedures, such as vascularized nerve grafting, nerve conduits, allografts and nerve transfers, can be successfully used in some cases. The current focus in the field is the development of nerve conduits. Textile technologies represent a promising field in creating nerve conduits, given the ease of the manufacturing process, the affordable production cost and good mechanical properties.