Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Due to its high incidence rate and often long-term sequelae, TBI contributes significantly to increasing costs of health care expenditures annually. Unfortunately, advances in the field have been stifled by patient and injury heterogeneity that pose a major challenge in TBI prevention, diagnosis, and treatment. In this review, we briefly discuss the causes of TBI, followed by its prevalence, classification, and pathophysiology. The current imaging detection methods and animal models used to study brain injury are examined. We discuss the potential use of molecular markers in detecting and monitoring the progression of TBI, with particular emphasis on microRNAs as a novel class of molecular modulators of injury and its repair in the neural tissue.