Quetiapine is an atypical antipsychotic approved by the FDA (Food and Drug Administration) for use in the treatment of schizophrenia, acute mania, and bipolar depression. Pharmacologically, it has antagonistic effects on serotonin 5-HT1A and 5-HT2A, dopamine D1 and D2, histamine H1, and adrenergic alpha1 and alpha2 receptors. In addition to reports of its use in schizophrenia and bipolar disorder, many studies have examined the use of quetiapine in the treatment of anxiety disorders and substance use disorders. In the treatment of patients with psychotic or bipolar disorder with a comorbid substance abuse disorder even though quetiapine was prescribed primarily for the treatment of the underlying psychotic symptoms, patients taking this medication reported a significant reduction in substance use. Yet, there are also case reports of quetiapine abuse and dependence; in particular among prisoners and patients diagnosed with substance abuse. Though quetiapine should be used peroral, it is also used intranasally and intravenously in these patient groups. Moreover, in some cases quetiapine is combined with other substances, such as cocaine or marijuana, to increase sedation. This abuse of quetiapine is thought to occur due to the anxiolytic and sedative effects of the drug. There are no controlled studies on quetiapine dependence in the literature and it remains unknown whether or not quetiapine causes dependence. This review aimed to present all published case reports on quetiapine abuse and to discuss the possible mechanisms that underlie its abuse and dependence.