All antipsychotic medications attenuate the symptoms of psychosis by interacting with dopamine D2 receptors and reducing dopamine-mediated neurotransmission. However, long-term antipsychotic treatment can produce neuroadaptations that are thought to lead to dopamine supersensitivity. In patients with schizophrenia, this dopamine supersensitivity could compromise treatment efficacy, promote relapse to psychosis and trigger movement disorders. Such effects have been seen in patients treated with either typical or atypical antipsychotics. In non-human animals, chronic exposure to antipsychotic medications, using clinically pertinent doses and modes of administration, can also evoke dopamine supersensitivity. This is indicated by an augmented behavioural response to dopamine agonists and tolerance to the antipsychotic-like effects of ongoing treatment. Here, we first describe antipsychotic-evoked dopamine supersensitivity in patients with schizophrenia and in laboratory animals. We then review approaches to prevent or reverse antipsychotic-evoked dopamine supersensitivity, based on preclinical animal studies. This evidence suggests that using atypical antipsychotics and regular but intermittent (versus continuous) antipsychotic dosing/D2 receptor occupancy is significantly less likely to produce dopamine supersensitivity. Lastly, we discuss potential neurobiological mechanisms. These include changes at the D2 receptor, but also other changes within and outside of the dopamine system. We conclude that in parallel to the search for new antipsychotic molecules, we need to better understand how different dosing regimens with currently used medications influence long-term outcome. There is also a pressing need to better characterize the development and expression of dopamine supersensitivity in humans. This will help determine the treatment strategies least likely to evoke dopamine supersensitivity. This article is part of the issue entitled 'Special Issue on Antipsychotics'. Copyright © 2019 Elsevier Ltd. All rights reserved.