Clozapine is the only agent approved for treatment-resistant schizophrenia, but is underprescribed. Its adverse drug event (ADE) profile and patient monitoring requirements can discourage its use, but the benefits of clozapine generally outweigh its risks, as most ADEs are manageable. Careful patient assessment, gradual titration, minimum effective dosages, therapeutic drug monitoring and checks of neutrophils, cardiac enzymes and ADE symptoms are recommended. Neutropenia is common but does not necessarily warrant permanent clozapine cessation.