Although great advances have been made in the pharmacotherapy of schizophrenia, many patients are still not taking full advantage of the beneficial effects of antipsychotic drugs. This is largely a result of the low levels of compliance. Conventional antipsychotics have little efficacy against negative symptoms, and so many patients with schizophrenia are refractory to treatment with these drugs. Additionally, clinically effective doses of conventional antipsychotics can actually aggravate negative symptoms through the development of extrapyramidal symptoms (EPS). Patients taking these drugs, therefore, often felt that the treatment was making them worse instead of better, and were reluctant to continue with it. The novel antipsychotics offer great potential for improving compliance. Clinical trials have shown that atypical drugs such as sertindole do not induce EPS, are effective against negative as well as positive symptoms and do not affect cognition. These observations have been reflected in postmarketing clinical experience, leading to recommendations that novel antipsychotics, such as sertindole, should be prescribed to first-episode patients. These patients would then not experience EPS and would be more likely to continue with their medication in the long term and thus avoid relapse. The major problems affecting compliance with pharmacotherapy for schizophrenia are outlined here showing, by means of case histories, how sertindole has benefited schizophrenic patients.