OBJECTIVE: This study aims to conduct a systematic review on the literature concerning relapse and non-adherence in schizophrenia patients in eight countries (Australia, Canada, France, Germany, Italy, Spain, UK, and US). METHODS: As of September, 2004, a literature search was performed in a number of databases including MEDLINE (1966-2004), EMBASE (1980-2004), PsycINFO (1967-2004), Cumulative Index to Nursing and Allied Health Literature (1980-2004) and other health technology assessment databases. Of the 1000 retrieved articles, around half were eventually reviewed in full text. RESULTS: Although definitions and measures of adherence and relapse between studies were very diverse, the rate of relapse in schizophrenia appeared to be from 40% to 55% for patients not taking the medication, and 14% to 30% for stabilized patients maintained on medication. Conventional antipsychotics tended to have higher rates of relapse than atypical antipsychotics. Most relapses tended to occur within the first year and, as such, many studies had a short follow-up period. The medication adherence rate for patients with schizophrenia ranged from 20% to 90%. This review has found that adherence is affected by environmental factors (e.g. social support), medication factors (e.g. side effects or lack of efficacy), doctor-patient relationship (e.g. lack of knowledge concerning the illness), forgetfulness, and treatment factors (e.g. medication regimes that are too complex). There was substantial evidence that depot medication aids patient adherence. Because current depot medications are available for conventional antipsychotics and risperidone, it was suggested that considerable advantages may be observed when more atypical antipsychotics are used in depot form. CONCLUSION: Relapse and non-adherence to antipsychotic agents in schizophrenia patients are quite prevalent and associated with adverse consequences. Furthermore, because treatment adherence appears to be strongly linked with relapse in schizophrenia, it is important that treatment interventions continue to address the problem of medication non-adherence.