This chapter presents the rationale for the primary effectiveness outcome and results for the randomized phases of the study. Effectiveness studies of any treatments for a chronic disease such as schizophrenia must incorporate a longer term view of the treatments' effects. A primary goal of such effectiveness studies is to determine the durability of the treatments. These studies examine whether the treatments continue to provide therapeutic benefit over the course of illness. To ensure maximum generalizability, few patients should be excluded from effectiveness studies. As symptom reduction remains an important goal of antipsychotic treatment and is the typical outcome in antipsychotic drug trials, the chapter discusses the results of how olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone compared in their effects on the core psychopathology of schizophrenia. CATIE findings on effectiveness and symptom reduction are consistent with many careful meta-analyses.