The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was undertaken to provide a valid assessment of the differences between conventional and atypical antipsychotics and among the atypicals themselves in patients with schizophrenia. The CATIE investigators reported that while none of the study medications were ideal, olanzapine was the most effective in terms of treatment discontinuation, and there were no significant differences in effectiveness between the conventional antipsychotic perphenazine and the atypicals quetiapine, risperidone, and ziprasidone. Each drug differed slightly in rates of side effects, with more patients discontinuing perphenazine due to extrapyramidal side effects and more patients discontinuing olanzapine due to weight gain and metabolic effects. In order for data from phase 1 of the CATIE study to be interpreted within the appropriate context, physicians must understand how aspects of study design and statistical methods affect interpretation, and how this trial weighs against other data in the literature. This article enumerates the factors that complicate our understanding of the CATIE results and compares these findings with those from previously published meta-analyses. It is clear that therapeutic and side effects of antipsychotics vary from person to person. The goal of schizophrenia management is to maintain pharmacotherapeutic efficacy and tolerability over the long-term in order to maximize treatment adherence and benefits. What should emerge from CATIE is a renewed commitment to tailor schizophrenia treatment to the individual patient for long-term management.