This chapter reviews findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study as it compares the effects of olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone on psychosocial functioning as measured on the Quality of Life Scale (QLS). In assessing psychosocial functioning, it was hypothesized that improvement would be different among treatments. The CATIE study was initiated by the National Institute of Mental Health (NIMH) to determine the effectiveness of antipsychotic drugs. For the Psychosocial Functioning Study presented in this chapter, we hypothesized that there would be differences among olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone in improvement in psychosocial functioning as measured by the QLS total scale. The QLS is a clinician-rated scale of social functioning, interpersonal relationships, and psychological well-being, originally developed to measure schizophrenic deficit syndrome. Many diverse approaches to evaluate psychosocial functioning and quality of life for individuals with schizophrenia make comparisons across schizophrenia studies difficult.