This review explores the latest advancements in traumatic brain injury (TBI) research, focusing on biomarkers and therapeutic targets. Traumatic brain injuries are a major global health issue, causing significant morbidity and mortality. TBIs can be classified as mild, moderate, or severe, with mild TBIs (mTBIs) being the most common. Biomarkers such as neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) have shown prognostic value for cognitive outcomes and are being used to develop personalized treatment strategies. These biomarkers are also being used to monitor treatment response and predict outcomes in TBI patients. Recent studies have shown that biomarkers like UCH-L1 and GFAP have been approved by the FDA as the first blood-based biomarker for TBI, known as the Brain Trauma Indicator (BTI). These biomarkers are sensitive to various types of trauma and can help in diagnosing and predicting outcomes in TBI patients. Additionally, studies have shown that these biomarkers can be used to differentiate between resolving and non-resolving trauma cases, with S100B remaining stable during the season, indicating its reliability as a biomarker of inconclusive sport-related concussion. In terms of therapeutic approaches, the most promising strategies target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce the impact of TBI and aid in neurological rehabilitation. Recent research has also focused on the role of extracellular vesicles (EVs) in TBI, with studies showing that EVs can be used to detect TBI and PTSD processes. Additionally, the use of biomarkers such as beta-synuclein and the analysis of EVs incorporating NF-L, GFAP, and others offer new perspectives in understanding the nature and dynamics of TBIs. The review also highlights the importance of neuroprotection in TBI treatment, with a focus on modulating biological pathways to minimize neuronal damage and enhance recovery. Research has shown that compounds that reduce brain damage, neuronal loss, and microglial activation can enhance long-term neurological functions. Additionally, studies have investigated the relationship between structural brain damage and functional impairment in both experimental and clinical settings, emphasizing the need for neuroprotective and restorative strategies to improve outcomes for TBI survivors. The review concludes that the identification of biomarkers and the development of targeted therapeutic approaches are crucial for improving the diagnosis, prognosis, and treatment of TBI.This review explores the latest advancements in traumatic brain injury (TBI) research, focusing on biomarkers and therapeutic targets. Traumatic brain injuries are a major global health issue, causing significant morbidity and mortality. TBIs can be classified as mild, moderate, or severe, with mild TBIs (mTBIs) being the most common. Biomarkers such as neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) have shown prognostic value for cognitive outcomes and are being used to develop personalized treatment strategies. These biomarkers are also being used to monitor treatment response and predict outcomes in TBI patients. Recent studies have shown that biomarkers like UCH-L1 and GFAP have been approved by the FDA as the first blood-based biomarker for TBI, known as the Brain Trauma Indicator (BTI). These biomarkers are sensitive to various types of trauma and can help in diagnosing and predicting outcomes in TBI patients. Additionally, studies have shown that these biomarkers can be used to differentiate between resolving and non-resolving trauma cases, with S100B remaining stable during the season, indicating its reliability as a biomarker of inconclusive sport-related concussion. In terms of therapeutic approaches, the most promising strategies target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce the impact of TBI and aid in neurological rehabilitation. Recent research has also focused on the role of extracellular vesicles (EVs) in TBI, with studies showing that EVs can be used to detect TBI and PTSD processes. Additionally, the use of biomarkers such as beta-synuclein and the analysis of EVs incorporating NF-L, GFAP, and others offer new perspectives in understanding the nature and dynamics of TBIs. The review also highlights the importance of neuroprotection in TBI treatment, with a focus on modulating biological pathways to minimize neuronal damage and enhance recovery. Research has shown that compounds that reduce brain damage, neuronal loss, and microglial activation can enhance long-term neurological functions. Additionally, studies have investigated the relationship between structural brain damage and functional impairment in both experimental and clinical settings, emphasizing the need for neuroprotective and restorative strategies to improve outcomes for TBI survivors. The review concludes that the identification of biomarkers and the development of targeted therapeutic approaches are crucial for improving the diagnosis, prognosis, and treatment of TBI.