The high incidence of concussion in contact sports provides a unique opportunity to collect data to characterize mild traumatic brain injury. This paper outlines a macro to micro approach in which the organ level response of the head is analyzed through head acceleration data from human volunteers and the tissue level response is analyzed through finite element analysis of these data. The helmets of Virginia Tech football players are instrumented with multi-accelerometer measurement devices to record linear and rotational head accelerations for every impact during a game or practice. These impacts are then modeled using the Simulated Injury Monitor (SIMon) finite element head model. Cumulative strain damage measure was investigated for the impacts resulting in the high linear and rotational accelerations. The effect of head impacts on functional performance in football players is also investigated to identify any cognitive effects from repetitive sub-concussive impacts. A better understanding of the effects of head impacts and the mechanisms of brain injury will likely result in insight to future head injury prevention methods and cellular research on brain injury.