Opioid use disorder is currently viewed as a chronic disease characterized by specific drug-seeking behaviors and compulsive use patterns. In general, these behaviors are difficult to control, and occur despite harmful consequences to the user, but not every person who is exposed to an opioid becomes addicted. The disease of addiction is complex and multifactorial and, as of this writing, a single factor has not been identified that can either accurately predict or quantify the risk that a given individual will develop opioid use disorder. Like most diseases, there is a combination of factors at play, which can influence the risk for addiction. The more risk factors a person has, the greater the chance that exposure to opioids will lead to addiction. Conversely, the fewer risk factors an individual has, the less likely that exposure will result in opioid use disorder. Specific risk factors discussed in this chapter include biological (genetic predisposition), environmental (exposure during critical points in development) and social factors such as accepted use within certain communities and variable access to medical care for members of different socioeconomic status.