Misuse of prescription opioids has substantially increased in the past decade among the general population, including among university students. Relative to the literature concerning opioid misuse among the general population, little information is available regarding the college student population. Objective: The purpose of the present study was to conduct a systematic review of the literature concerning the prevalence of prescription opioid misuse among the university student population. Results: The lifetime estimate for prescription opioid misuse among general populations of students ranged from 4% to 19.7%, with higher estimates for special student populations. Students most at risk for misuse of prescription opioids are those who report higher rates of psychological distress, depression, and suicidal thoughts and behaviors, and white, male students who use alcohol and illicit drugs. Conclusions: Findings from this study underscore the need for opioid prevention and intervention programs on university campuses.