Assessing that the efficacy of a cancer therapeutic is an integral part of its path to regulatory approval, we review the history that led to our current assessment method, Response Evaluation Criteria in Solid Tumors (RECIST). We describe the efforts of Moertel and Hanley to standardize response assessments in lymphoid malignancies and how this was adapted in the World Health Organization (WHO) criteria. Two decades later, RECIST was advanced to streamline WHO and improve its reproducibility. We describe the ways in which thresholds established by Moertel and Hanley to provide accuracy and reproducibility evolved to become measures of efficacy and why they have been valuable. While we recognize RECIST is far from perfect-in need of modification as a measure of efficacy for some agents and in some diseases-for the majority of solid tumors, it is very valuable. We argue that over time, the efficacy thresholds established by WHO and then RECIST have proved their worth, and we summarize 10 years of U.S. Food and Drug Administration (FDA) approvals in solid tumors to support our position that current RECIST thresholds should be retained.