Omega-3 polyunsaturated fatty acids (PUFAs) are compounds that have a structural role in the nervous system and are essential for neurodevelopment. Results obtained with docosahexaenoic acid and eicosapentaenoic acid show therapeutic potential in neurotrauma. Traumatic brain injury (TBI) and spinal cord injury (SCI) can lead to major disability and have a significant socioeconomic cost. Thus, there is an unmet need for acute neuroprotection and for treatments that promote neuroregeneration. Acute administration of omega-3 PUFAs after injury and dietary exposure before or after injury improve neurological outcomes in experimental SCI and TBI. The mechanisms involved include decreased neuroinflammation and oxidative stress, neurotrophic support, and activation of cell survival pathways. This review raises questions that must be addressed before successful clinical translation.