The fruit fly Drosophila melanogaster has been a powerful model to study axonal biology including axon degeneration and regeneration (Brace et al., J Neurosci 34:8398–8410, 2014; Valakh et al. J Neurosci 33:17863–17,873, 2013; Xiong and Collins J Neurosci 32:610–615, 2012; Xiong et al. 191:211–223, 2010). Both adult and larval injury models have been developed in the fruit fly. This chapter focuses on in vivo and ex vivo methods developed for studying axon degeneration in Drosophila larvae. Additional models have been developed in the adult fly including injury models of olfactory receptor neurons in the brain and a model of axonal degeneration of sensory axons in the wing (Fang and Bonini, Annu Rev. Cell Dev Biol 28:575–597, 2012; Hoopfer et al. Neuron 50:883–895, 2006; Neukomm et al. Proc Natl Acad Sci U S A 111:9965–9970, 2014).