The treatment of nonresponsive schizophrenia poses perennial problems. The situation is made yet more complex when the great variety of patient types, their social background, family circumstances and psychosocial requirements are taken into account. The comparative lack of response to neuroleptic therapy seen in some patients, especially those with minimal structural brain changes, further complicates the problem, provoking—as such therapy may—more EPS than are normally seen in patients without more obvious physical changes in brain structure. Until recently, the treatment of nonresponsive schizophrenia has tended to involve switching from one neuroleptic (usually a “highpotent” agent) to another of different chemical structure. However, as these “typical” neuroleptics occupy D2 receptors, the rationale for using a less conventional antipsychotic, such as clozapine, is increasingly appreciated in the management of the treatment-refractory schizophrenic.