Unlike its central counterpart, the peripheral nervous system is well known for its comparatively good potential for regeneration following nerve fiber injury. This ability is mirrored by the de novo expression or upregulation of a wide variety of molecules including transcription factors, growth-stimulating substances, cell adhesion molecules, intracellular signaling enzymes and proteins involved in regulating cell-surface cytoskeletal interactions, that promote neurite outgrowth in cultured neurons. However, their role in vivo is less known. Recent studies using neutralizing antibodies, gene inactivation and overexpression techniques have started to shed light on those endogenous molecules that play a key role in axonal outgrowth and the process of successful functional repair in the injured nervous system. The aim of the current review is to provide a summary on this rapidly growing field and the experimental techniques used to define the specific effects of candidate signaling molecules on axonal regeneration in vivo.