Opioid use disorder (OUD) is defined as a complex genetic disorder in which environmental and genetic factors are effective. Various genes have an impact on the stages of continuation, and cessation of substance use, but the effect of such a genetic profile depends on environmental triggers including family substance use, stress, and peer. Variations in genes encoding various proteins related to reward could affect not only the susceptibility to OUD and but also treatment responses of OUD by altering structure and/or function of proteins. Understanding the underlying mechanisms of polymorphisms is important to increase the effectiveness treatment of OUD. This chapter first describes opioids, OUD, neurobiology and treatment of OUD, and genetic variations and then gives an overview of single nucleotide polymorphisms that could be effective both in susceptibility to OUD and its treatment responses.