Neurons encounter a variety of insults that profoundly impact the function of the nervous system, from trauma (e.g., spinal cord injury) to neurodegenerative pathology (e.g., Alzheimer’s disease). The fate of injured neurons depends on their ability to respond and adapt. My laboratory aims to understand the mechanisms and consequences of neuronal injury signaling. This understanding will drive the development of new therapeutic strategies to enhance repair pathways and reduce pathological responses. Axonal damage provides an invaluable system for these investigations, providing: (1) distinct examples of the strikingly contrasting outcomes of injury signaling, from functional axon regeneration to extensive neurodegeneration; (2) technical simplicity of both in vitro and in vivo models, including genetic manipulation; and (3) application to persistent challenges in neurology and neurosurgery. Our studies have identified the Dual Leucine-zipper Kinase (DLK) as a master regulator of both regenerative and apoptotic responses to optic nerve damage and of multiple axonal stress response pathways, including JNK and PERK signaling. Manipulation of DLK therefore represents an appealing approach for exploiting the intrinsic neuronal injury response for therapy.