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Aripiprazole is an atypical antipsychotic used for schizophrenia, manic and mixed episodes associated with bipolar I disorder and as adjunctive therapy for major depressive disorder. It functions as a partial agonist at dopamine D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptor. The most recent results obtained from scientific research showed that dopaminergic mechanisms are involved in motivation, reward, and reinforcement of substance abuse. The use of aripiprazole and partial dopamine agonists could represent a novel strategy for normalizing dopamine neurotransmission. Many studies in the last few years have highlighted aripiprazole as a potential candidate for the treatment of different types of substance dependence. This review aims to describe recent scientific research using aripiprazole in different substance abuse disorders (i.e., alcoholism, cocaine, amphetamine and nicotine use). Furthermore, the efficacy of aripiprazole compared to other pharmacological therapies will be described. Given the low number of studies, the frequent absence of placebo or active comparators, and the low statistical power of the studies, a clear conclusion about the use of aripiprazole in alcohol/substance dependence cannot be drawn. Therefore, we suggest the need for further studies, preferably randomized and placebo-controlled.