Spinal cord (SC) injury in humans has often irreversible consequences. The impaired regenerative response in mammals seems to result from the formation of a glial and fibrotic scar at the injury site that is thought to inhibit regeneration. In contrast to mammals, the zebrafish SC has the remarkable capacity to recover motor and sensory functions after injury. This ability seems to stem from the supportive microenvironment, without the formation of a glial or fibrotic scar, that allows neuronal differentiation and regrowth of severed axons. It is therefore important that when thinking about SC regeneration, one should consider the influence of the microenvironment at the injury site, an aspect that has been understudied. I will discuss similarities and differences concerning neural stem cells vs. microenvironment between zebrafish and mice SCs.