Therapy-resistance for positive symptoms is one of the most important problems that occurs with the medical treatment of schizophrenia. In the past years, clozapine has proven its effectiveness in this area and has been included in the treatment protocols and guidelines. Because of the risk of agranulocytosis with this compound and the intensive laboratory controls to be done, several studies have been performed with the new antipsychotics risperidone and olanzapine as alternative treatments. A review of the literature suggests that both drugs are as effective as the classic antipsychotics for therapy-resistant patients. A switch to risperidone or olanzapine possibly would be a alternative for those patients who have favourable effects on a low dose of clozapine. Furthermore the new antipsychotics have less side effects and ameliorating effects on negative and cognitive symptoms, so contributing to overall improvement in chronic schizophrenic disorders. However, in case of persistent positive symptopathology, clozapine remains the golden standard. The new antipsychotics should be included in treatment protocols before clozapine.