The argument is presented here that, while there exists considerable correlative evidence supporting the oxidative stress hypothesis of aging, key experiments to test this hypothesis using Drosophila transgenics overexpressing Cu,Zn-SOD fall short in providing validation. In particular, significant life span extensions tend to be observed when the backgrounds of the control flies are relatively short-lived, suggesting that bolstering antioxidative defenses is only effective in compromised genetic backgrounds. Other shortcomings of the transgenic approaches adopted to date will be summarized.