Abstract: Lampreys are one of the most ancient extant vertebrates and they have become an animal model of interest for the study of spontaneous axon regeneration after a traumatic central nervous system injury. Contrary to most mammals, lampreys recover locomotion after a complete spinal cord injury (SCI). During recovery from SCI, some of the descending axons in lampreys regenerate through the injury site and reinnervate caudal levels of the spinal cord. Interestingly, the brainstem of lampreys contains 36 giant descending neurons that can be identified individually and that show very different survival and regenerative abilities after a complete SCI (Jacobs et al., 1997; see Barreiro-Iglesias, 2015), even when their axons are found in similar locations in a spinal cord that is permissive for axonal regrowth. Some of these identifiable neurons are considered “good” regenerators (they regenerate their axon more than 55% of the times) and others are considered “bad” regenerators (they regenerate their axon less than 50% of the times) (Figure 1). This offers a model in which the intrinsic mechanisms regulating neuronal survival and axonal regrowth can be studied in vivo and at the level of individual neurons. First, one can use this model to find genes showing differential expression between “good” and “bad” regenerator neurons, and then try to perform functional studies by manipulating their expression or their action. As in any other animal model, drugs can be used for this purpose (Fogerson et al., 2016; Romaus-Sanjurjo et al., 2018; Sobrido-Cameán et al., 2019, 2020), but ideally genetic manipulations are also needed to confirm drug effects or to manipulate the expression of genes for which no drugs are available.