Abstract Introduction: Addictive substances act on a number of neurotransmitter systems, and the end result of this action is the activation of the reward system in the brain. The cellular and neuronal mechanisms that underlie addiction have long been searched for. One of such neurotransmitters is dopamine, a catecholamine synthesized in neurons located mainly in the midbrain. Material and method: The available literature was reviewed on the Pubmed platform and from other sources. The analysis included original studies, reviews. The aim of the study was to review the literature on the relationship between the DRD2 gene and the occurrence of substance addiction. Discussion: This work presents several currently discussed biological mechanisms, especially at the molecular and genetic level, involved in the process of addiction to various psychoactive substances. They discovered the brain structures that are most at risk, as well as other neurotransmitter systems and receptor proteins through which they can exert their pathological effects. It has also been established that exposure to psychoactive substances causes significant changes in expression in over 100 genes (including genes for dopaminergic, serotonergic and signaling pathways). The DRD2 receptor (present, among others, in the nucleus accumbens) plays an important role in the reward system, in the transmission of information. The weakening of this conductivity is a significant risk factor for the onset of clinical features that are associated with reward system deficiency syndrome. The expression of the D2 receptor gene may take up to 2 isoforms: short D2S and long D2L. Conclusions: Further research at the molecular level may result in the modification of psychotherapy and pharmacotherapy in terms of their personalization.