Adult zebrafish, in contrast to mammals, are capable of functional regeneration after spinal cord injury. Regeneration studies in zebrafish benefit from the model status of this vertebrate for research on developmental biology. This model status has helped to make available molecular tools such as genetic manipulation, expression profiling and gene knock-down techniques. Behavioral recovery after spinal injury is clearly quantifiable in zebrafish using different tests. The anatomical basis for behavioral recovery is supported by a surprising heterogeneity in axon regrowth and gene expression in different neuronal populations. In addition, specific gene regulation in non-axotomized spinal neurons indicates plasticity of the spinal circuitry after injury, which may also contribute to behavioral recovery. Gaps in our understanding of the spinal network are being filled by several studies of the more simple spinal network found in larval zebrafish. Gene knock-down, interference with intracellular messenger systems and promoter analysis in neurons after lesion are all possible in vivo, demonstrating the experimental accessibility of the system. At the same time, environmental inhibitors of axon re-growth appear not to be prominent in fish. Thus, environmental conditions may not confound the study of neuronal reactions to axotomy. Zebrafish, therefore, offer the opportunity to perform in-vivo studies of the mechanisms that lead to successful recovery after spinal cord injury, from the molecular to the systems levels.