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Clozapine is considered to be the most efficacious drug to treat schizophrenia, but despite these benefits, clozapine prescriptions comprise only 2-10% of the total antipsychotic market for schizophrenia in the United States. It was introduced on the market in 1971 but was withdrawn in 1975 after reports of clozapine-induced agranulocytosis (CIA) in Finland. Due to its high efficacy in treatment-resistant schizophrenia, it was reapproved in 1990 by the FDA and health authorities in most other countries; however, regular hematological monitoring was required. The implementation of this monitoring system has successfully reduced the incidence of CIA from 1.3% to 0.4%. Currently 239 cases of agranulocytosis are registered at the FDA adverse drug reaction data bank. There have been certain attempts to predict agranulocytosis by genetic association studies in particular in the NADPH myeloperoxidase complex (1) and FC-gamma receptors (2). We could identify an association to the polymorphic myeloperoxidase, responsible for oxidative reaction in neutrophils. More recently, confirmatory studies in two independent cohorts of 33 and 49 CIA cases and 54 and 78 controls indicated that markers in the HLA system are highly significantly associated with the risk of CIA. HLA-DQB1 6672G>C was associated with CIA conferring an odds ratio of 16.9 (3). Currently a large consortium led by Duke University has aimed to collect a large sample of well defined cases of CIA in order to allow genome-wide association studies.