The use of 3D video games in memory rehabilitation has been explored very little. A virtual navigation task allows participants to encode the spatial layout of the virtual environment and activate areas involved in memory processing. We describe the rehabilitation of a 24-year-old man with traumatic brain injury presenting memory deficits, and evaluate the efficacy of a navigational training program measuring neuropsychological changes and fMRI modification cerebral activations. Memory improvement appears to be present both after navigational training and in follow-up testing. Furthermore, fMRI data suggest that this training may increase activation of the hippocampal and parahippocampal brain regions. The results suggest that intensive training in virtual navigational tasks may result in an enhancement of memory function in brain-damaged adults.