Concussion is a physiological injury to the extremely complex and dynamic human brain. Individual variability adds to the challenge of concussion management, and sports medicine practitioners recently have begun to realize the need for an individualized approach. Adequately assessing an athlete with concussion requires consideration of many risk factors, including age, gender, and certain comorbid conditions. Understanding how these factors may affect concussion risk and outcome is becoming an essential aspect of management. This article reviews what is known or assumed about how some of these risk factors affect concussion. We conclude by providing several key concepts that we feel are important to keep in mind when managing an athlete with concussion.