This article reviews the evidence of the effects of atypical antipsychotics other than clozapine in patients with schizophrenia that is resistant to treatment with conventional agents. Clozapine remains the one drug with proven efficacy in patients with severely refractory symptoms. However, while the drug is modestly effective in 30 to 70% of these patients, there are many who are either intolerant of, or unresponsive to, it.The initial hope that the new atypical antipsychotics would play a major role in treatment-resistant schizophrenia has not really materialised. Nevertheless, it is increasingly recognised that perhaps the majority of patients with schizophrenia have milder degrees of refractoriness − so-called ‘partial responders’ − and considerable evidence is emerging for an important role for risperidone, olanzapine and quetiapine in these patients. These drugs appear to have advantages over the conventional antipsychotics in terms of both efficacy and tolerability in these patients.More studies are required to establish optimal dosages of the atypical antipsychotics in patients with refractory symptoms, as well as whether some individuals respond differentially to a particular drug.