When treatments are known to be successful with good oncological outcomes for specific cancers, most patients will be prepared to accept the proposed therapy and its consequences on quality of life. But when multiple, equally effective treatments are available and uncertainty about their benefits prevails with a substantial risk of overtreatment, the balance of risks between benefit and harm from adverse effects can dominate decision making. Such is the case in clinically localized prostate-specific antigen (PSA)–detected prostate cancer. Men affected by prostate cancer realize increasingly that survival and prostate cancer recurrence rates alone are insufficient to allow sound clinical decisions to be made and that there are trade-offs between cancer control and adverse treatment effects. Two articles in this issue of JAMA by Barocas and colleagues1 and by Chen and colleagues2 address this important problem.