The recent advent of atypical antipsychotic medications has provided new clinical options and set higher expectations for the treatment of schizophrenia and other psychoses. Two such drugs, clozapine and risperidone, are currently employed in the United States. Researchers continue to fine-tune treatment with these agents and to seek possible new uses for them. For clozapine, refinements in use (optimal duration of trial, optimal dose, use of drug plasma level to optimize efficacy) are described, along with side effects and the specificity (or lack thereof) of the drug's action upon primary negative symptoms. Also discussed is use of clozapine in new subgroups of patients for example, those with first-episode schizophrenia, polydipsia syndrome, or a dual diagnosis. For risperidone, use in patients with first-episode schizophrenia, affective disorders, autism, and other disorders is described. Cost-benefit considerations are presented for both drugs. The psychosocial needs of patients taking these medications and the potential for synergy between novel antipsychotics and modern psychosocial therapies are also discussed.