Schizophrenia is a common, debilitating illness for which treatment is empirical and unsatisfactory. Intense efforts to identify etiological factors have been launched in order to facilitate rational therapy. Such efforts have included gene-mapping studies since a significant heritability has been proved. In common with other polygenic/multifactorial disorders, mapping efforts for schizophrenia pose daunting challenges. Faced with such complexities, attempts to detect genetic associations with pharmacological response have been initiated. Although intriguing associations have been reported, formal replication is required. Suggestions for the design of replicate studies are proposed. This review is restricted to studies that investigated response to clozapine (Clozaril®, Novartis) and other novel antipsychotic medications.