Iloperidone is an atypical antipsychotic that is approved for the treatment of adult patients with schizophrenia. In several large (n > 570 per trial), 4- or 6-week, double-blind, multinational, multicentre trials in adult patients with schizophrenia, recommended target dosages of oral iloperidone (6-12 mg twice daily) generally showed better efficacy than placebo, in terms of improvements in Positive and Negative Syndrome Scale (PANSS) total scores or Brief Psychiatric Rating Scale (BPRS) scores (primary endpoints) and also for most secondary endpoints, including PANSS subscale scores. In addition, pharmacogenomic studies identified single nucleotide polymorphisms (SNPs) that were associated with an enhanced response to iloperidone during acute treatment of schizophrenia. More limited data also support the role of these SNPs in enhancing responses to iloperidone during longer-term treatment. In a pooled analysis of three 52-week, double-blind, multinational, multicentre trials (n = 473), iloperidone treatment was shown to be equivalent to that with haloperidol, based on Kaplan-Meier estimates of the time to relapse (primary endpoint). Iloperidone was generally well tolerated and was associated with few extrapyramidal symptoms or changes in metabolic parameters in short- and longer-term clinical trials in adult patients with schizophrenia.