Traumatic brain injury (TBI) is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as development, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma (miR-425-p, -21, -93, -191 and -499) and cerebro-spinal fluid (CSF) (miR-328, -362-3p, -451, -486a) as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI (e.g., miR-21, miR-23b). MicroRNA profiling was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI (e.g., miR-21) have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups (children, adults, and elderly).