In schizophrenia, the objectives of long-term maintenance therapy are to achieve continuous relief from psychotic symptoms, to prevent relapse, to optimize patient functioning and improve quality of life. It is now generally accepted that atypical antipsychotic agents are more effective than conventional agents in achieving these goals over the short term. In order to define the role of atypical antipsychotics as maintenance treatment for schizophrenia, studies published between January 1994 and November 2005 that evaluated the long-term efficacy (> or =1 year) of atypical antipsychotics for the treatment of schizophrenia were reviewed as identified from literature researches using MEDLINE and EMBASE. The primary research parameters were 'atypical', 'antipsychotic', 'schizophrenia', 'relapse', 'long-term', 'maintenance' and 'efficacy'. Aspects of safety were also considered for these agents. Results from these long-term studies consistently demonstrated that atypical antipsychotics have substantial advantages over oral conventional antipsychotics as proven by fewer relapses, more effective symptom control and a lower incidence of movement disorders, although some atypical agents were associated with a higher incidence of weight gain. However, due to issues of compliance, the clinical advantage of oral atypical antipsychotics has often been limited. As such, the use of long-acting preparations of atypical antipsychotics, which provide consistent and sustained drug coverage, warrants further investigation for the successful long-term management of patients with schizophrenia.