Traumatic brain injury (TBI) is a major public health concern. TBI has two phases: a primary injury due to direct damage from a mechanical force applied to the head and a secondary injury due to cellular and molecular responses to the injury. Despite its significant burden on societies, decades of clinical trials have not yielded any FDA‐approved therapies for TBI. Insignificant endogenous repair and continued neuronal cell loss underlie the disability in TBI survivors. The advent of stem cell culture led to the notion that such cells could potentially replace lost cells. Examination of preclinical and clinical studies suggests that stem cell‐replacement approaches in TBI remain elusive. In contrast, stem cell transplantation appears to mitigate multiple TBI‐induced pathologies by modulating inflammation, angiogenesis and endogenous neurogenesis. Thus, transplantation‐based stem cell therapeutic approaches are a viable treatment option for TBI. Key Concepts Traumatic brain injury (TBI) is a major health concern with complex underlying pathology mechanisms and no FDA‐approved treatments to date. Stem cells, which can be obtained from different sources, have therapeutic properties that render them beneficial for treating various neurological and neurodegenerative diseases, including TBI. Stem cell‐based therapy has been utilised for the treatment of TBI and has shown to be a therapeutic promise in few preclinical and early phase clinical studies. Neural stem cells have neuro‐restorative properties that are promising for the treatment of various neurological and neurodegenerative disorders. Despite their promising therapeutic abilities, stem cell‐based therapies still face several hurdles that limit their efficacy as a treatment in TBI. More research is needed to perfect this treatment approach.

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