Oral paliperidone extended or prolonged release (Invega®) is an atypical antipsychotic, and is the first agent approved for the treatment of schizoaffective disorder. Paliperidone (or 9-hydroxyrisperidone) is the major active metabolite of the well known atypical antipsychotic risperidone, and its mechanism of action is thought to be the antagonism of dopamine D(2) and serotonin 5-HT(2A) receptors. The clinical efficacy of paliperidone was demonstrated in two 6-week, randomized, double-blind, placebo-controlled, multicentre trials in patients with schizoaffective disorder. One trial was flexible dose in design (3-12 mg/day) and the other was fixed dose in design (3-6 and 9-12 mg/day). Compared with placebo, the change from baseline at study end in the Positive and Negative Syndrome Scale (PANSS) total score (primary endpoint) was significantly greater with paliperidone 3-12 mg/day in one trial and with 9-12 mg/day (but not 3-6 mg/day) in the other trial. However, pooled analyses reported a significantly greater change in PANSS total score across all paliperidone dosages than with placebo. Paliperidone was generally well tolerated in the 6-week trials, and no unexpected adverse events were reported. The most commonly reported treatment-emergent adverse events were headache, tremor, dizziness, insomnia, nausea, akathisia, dyspepsia, hypertonia, somnolence and sedation. Although long-term efficacy and tolerability data and comparisons with other antipsychotics are needed, paliperidone appears to be a useful agent for the short-term management of patients with schizoaffective disorder.