Antipsychotic medications are mainstays in the treatment of schizophrenia and a range of other psychotic disorders.Recent meta-analyses of antipsychotic efficacy and tolerability have been included in this review, along with key papers on antipsychotic use in schizophrenia and other psychotic illnesses.The heterogeneity in terms of individuals' response to antipsychotic treatment and the current inability to predict response leads to a trial-and-error strategy with treatment choice. Clozapine is the only effective medication for treatment-resistant schizophrenia.There are a significant number of side effects associated with antipsychotic use. With a reduction in the frequency of extrapyramidal side effects with the use of second-generation antipsychotics, there has been a significant shift in the side effect burden, with an increase in the risk of cardiometabolic dysfunction.There exist small and robust efficacy differences between medications (other than clozapine), and response and tolerability to each antipsychotic drug vary, with there being no first-line antipsychotic drug that is suitable for all patients.A focus on the different symptom domains of schizophrenia may lead to endophenotypic markers being identified, e.g. for negative symptoms and cognitive deficits (as well as for positive symptoms) that can promote the development of novel therapeutics, which will rationally target cellular and molecular targets, rather than just the dopamine 2 receptor. Future developments will target additional processes, including glutamatergic, cholinergic and cannabinoid receptor targets and will utilize personalized medicine techniques, such as pharmacogenetic variants and biomarkers allowing for a tailored and safer use of antipsychotics.