This paper aims to give a brief overview on traumatic brain injuries’ (TBIs) main pathophysiological mechanisms, to summarize the current available therapeutic strategies and offer a glimpse at possible future advancements in the field. The impact of TBI on health care systems and society is tremedous. While the surgical and intensive care management are relatively well standardized for acute TBI, subsequent, therapeutic interventions remain at the physician’s choice/ professional skills, and their clinical utility is still questionable. Previous experience and numerous trials have failed to demonstrate a consistent benefit from therapies like corticosteroids, lazaroids, nsaids vasodilators, glutamate blockers, immune modulators, or general hypothermia. Novel achievements in neuroprotection are now expected from developing anti-apoptotic agents (such as caspase and/or calpain inhibitors), from more potent antioxidants, cholinergic agents, alpha blockers from researching various physiologic substances, like melatonin, protirelin, inosine, progesterone, and including from regenerative medicine and physiatric, assisstive technology/ bioengineering advancements.