Neuroleptic drugs remain a critical component of the treatment of schizophrenia. Although their use in other conditions such as bipolar disorders and organic mental disorders is also widespread, further research is necessary to validate specific indications and to assess benefit-to-risk ratios. In recent years substantial attention has been focused on establishing minimum effective dosage requirements for both acute and long-term treatment of schizophrenia. Considerable progress has been made in this area. In addition, alternative maintenance-treatment strategies such as targeted or intermittent neuroleptic therapy have been studied. The management of patients who fail to respond to an adequate trial (or trials) of neuroleptic drugs continues to be an enormous clinical challenge. Few data are available on which to base subsequent treatment decisions. Recent research with clozapine suggests that this compound may be helpful in some such individuals, but further efforts to establish other potentially effective treatment strategies for treatment-refractory patients should receive a high priority.