In this commentary article we describe our clinical experience and provide our views on the use of quetiapine in the treatment of patients with acute exacerbations of schizophrenia. Some patients with acute schizophrenia may require parenteral medication; however, we believe that oral antipsychotics, either alone or in combination with other medications, have a key role to play as an initial and/or subsequent pharmacotherapeutic intervention. Quetiapine has beneficial calming properties and successfully treats the symptoms of aggression, anxiety and hostility that can accompany acute exacerbations of schizophrenia. Based upon a review of published findings, data presented at recent international psychiatric congresses and our clinical experience, we propose that a more rapid initiation schedule (for example, 400 mg by Day 2, increasing to 600 mg/day by Day 3 and often up to 800 mg/day by Day 4, or in severe cases 300 mg on Day 1, 600 mg on Day 2 and 900 mg on Day 3) than that currently described in quetiapine prescribing information can be used to provide safe, effective treatment in hospitalised patients with acute schizophrenia. (Note that lower doses are used in patients with first-episode schizophrenia.) Furthermore, while current prescribing information recommends that quetiapine be administered at doses up to 750 mg/day (800 mg/day in the USA and Canada), there is growing evidence that dosing up to 1600 mg/day of quetiapine has been well tolerated in some patients. In general, newer antipsychotics have superior tolerability profiles compared with conventional agents; however, clear differences in tolerability exist among the new generation antipsychotics. Quetiapine has an excellent tolerability profile offering high patient acceptability that, in turn, may promote patient adherence to medication and an improved quality of life. As such, we consider quetiapine to be a first-choice antipsychotic for the treatment of acute exacerbations of schizophrenia.