The current literature describing the pharmacokinetics of the atypical antipsychotics clozapine and risperidone is reviewed, and discussion on the clinical significance of these data is presented. These drugs are well absorbed when taken orally but are poorly bioavailable because of presystemic elimination. They are highly cleared by hepatic metabolism involving specific P450 isozymes. Risperidone elimination produces a potent active metabolite. Neither of the drugs has received extensive study related to drug-drug interactions, but several are potentially important because a purported therapeutic plasma concentration range is proposed for clozapine and a possible curvilinear dose response relationship has been reported for risperidone. The current clinical pharmacokinetic database for these atypical antipsychotics suggests that much can be learned with additional study that would be of value in individualizing their dosage regimens.