Subjective response to neuroleptics in patients with schizophrenia is reviewed in terms of its validity and measurement. Evidence is presented to support a correlation between altered subjective state on neuroleptics, and therapeutic outcome and medication compliance. Factors that have been implicated in the genesis of such altered subjective states include demographics, psychiatric characteristics, type and dose of neuroleptic, extrapyramidal symptoms (particularly akathisia), depressive states, and patients' values and attitudes toward health and illness. Factors that may contribute to lack of interest in researching subjective experiences of schizophrenia patients on medications are reviewed, and methodological improvements in study design are proposed to enhance our understanding of this phenomenon. Such understanding may help us to better appreciate the many factors that contribute to variability of responses to neuroleptic therapy in patients with schizophrenia and also help us to develop more effective treatment strategies.