The chapter summarises the pathophysiological response to peripheral nerve injury and subsequent regeneration reactions, with a particular focus on nerve gap injuries. To repair and bridge the tissue defects, nerve guidance conduits (NGCs) have been proposed as an alternative approach to autografts. Designing optimal NGCs requires development of (i) the conduit body, (ii) intraluminal structures and (iii) addition of regeneration promoting biological components to the lumen. The chapter provides a historical background to this research area and describes the current state of the art with a range of biomaterial constructs, which can be supplemented with Schwann cells or alternatively a variety of stem cells.