Traumatic brain injury (TBI) is the primary cause of death and disability for 18- to 45-year-olds. High-level mobility is important for many of the social, leisure, sporting, and employment roles of young adults. The aim of these case reports was to evaluate a conceptual framework for retraining high-level mobility after TBI. The progression of 2 patients who had sustained a severe TBI but had contrasting clinical presentations was monitored over 6 months. Patient 1 presented with left hemiplegia following a TBI 10 years earlier, whereas patient 2 presented with ataxia 2 months following a TBI. Quantitative gait analysis and clinical measures of mobility were used to evaluate outcomes of a 6-month intervention phase. Intervention strategies were based on a conceptual framework comprising 2 main elements: (1) the hierarchical ordering of high-level mobility tasks and (2) the key biomechanical features of able-bodied running. Both patients achieved the ability to run by the end of the intervention phase. Patient 1 displayed improved gait symmetry associated with improved high-level mobility, despite the long-standing duration of his injury. Patient 2 demonstrated improved postural control and stability in gait that resulted in an ability to run, skip, hop, and jump. Findings of these case reports provide evidence supporting "proof of concept" that clinical interventions can lead to improvement in high-level mobility following severe TBI.