In the pre-clinical view, the study of peripheral nerve repair and regeneration still needs to be carried out in animal models due to the structural complexity of this organ which can be only partly simulated in vitro. The far most used experimental model is based on the injury of the sciatic nerve, the largest nerve trunk in mammals. In this paper, the potential application of the sciatic nerve injury model in pre-clinical research is critically reviewed. This paper is aimed at helping researchers in properly employing this in vivo model for the study of nerve repair and regeneration as well as interpreting the results in a clinical translation perspective.