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This clinical review summarizes the pharmacological characteristics, efficacy, and tolerability of asenapine, iloperidone, and lurasidone, the most recently approved antipsychotics in the treatment of schizophrenia. Newer agents have the task of distinguishing themselves for clinical use based on patient-relevant characteristics; some provide specialized features. The agents reviewed here are similar in overall clinical efficacy and tolerability, as well as being in a low risk for weight gain and metabolic syndrome, but are different in terms of formulation, schedule of administration, and particular side effects. Based on these distinguishing characteristics, we offer recommendations for the optimal clinical use of each drug.