The laboratory mouse has emerged as a primary model organism for studying axon regeneration after experimental spinal cord injury, owing to its genetic amenability. Mutant mouse models are contributing significantly to our understanding of the molecular mechanisms of axon regeneration failure in the adult mammalian central nervous system (CNS), in particular regarding the role of axon-growth inhibitors. Here, we discuss recent advances in understanding axon regeneration failure that have been made using genetically modified mice, focusing on the inhibitory influences in the CNS, and we illustrate the advantages of using the mouse as a surrogate organism to study axon regeneration and spinal cord repair.