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Traumatic brain injury (TBI) leads to a cascade of pathological processes in the brain such as oxidative stress and hyperexcitability which contribute to neuronal death and ultimately long-term cognitive/functional impairments. One such process involves zinc dyshomeostasis, which is implicated in aging and the development of several neurodegenerative diseases such as Alzheimer's disease and more recently chronic traumatic encephalopathy. While some studies have shown that TBI can cause zinc deficiency, others have reported zinc accumulation in the brain. This has led to inconclusive data in relation to the efficacy of zinc supplementation following TBI, thereby providing an opportunity to explore other therapeutic avenues such as zinc chelator and chaperone-like drugs. As such, this chapter addresses the gap in the literature regarding whether zinc is neuroprotective and/or neurotoxic and examines the …