This paper is dedicated to the memory of Laurence P. Clarke, PhD, whose vision helped shape not only the LUNGx Challenge but also, more importantly, the broader imaging research landscape of open science, consensus building, and collegiality that provides context for the significance of grand challenges. He worked tirelessly to advance research objectives by helping to surmount obstacles, building bridges across institutions or governmental agencies, and selflessly advocating on behalf of other investigators who shared his devotion to imaging research. Dr. Clarke’s career had a dramatic impact on the current state of medical imaging research around the world. His leadership was profound, his scientific contributions substantial, his intentions sincere, his humor infectious, and his personality genuine; he will be greatly missed by all his coauthors, colleagues, and friends. The authors would like to express their appreciation to Angela Keyser and Shayna Knazik from the AAPM and Diane Cline and Sandy Hoelterhoff from the SPIE for their assistance in making this challenge a reality. The LUNGx Challenge was supported by SPIE, AAPM, and NCI. The authors are grateful to the groups that participated in the LUNGx Challenge, including groups led by Yoganand Balagurunathan (H. Lee Moffitt Cancer Center), Wookjin Choi (University of Maryland School of Medicine, now at Memorial Sloan Kettering Cancer Center), Samuel Hawkins (University of South Florida), Xiaojie Huang (GE Global Research), Lyndsey Pickup (Mirada Medical, now at Optellum), Jiangdian Song (Northeastern University, China), Yubing Tong (University of Pennsylvania), and Rafael Wiemker (Philips Research Labs Hamburg). These participating groups deserve recognition for their work to develop their lung nodule classification methods and for their contributions to the success of the Challenge. The authors would like to thank the radiologists who participated in the observer study: Prachi Agarwal, MD, Aamer Chughtai, MD, Jonathan Chung, MD, Heber MacMahon, MD, Steven Montner, MD, and Smita Patel, MD. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This manuscript has been authored in part by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The US Government retains and the publisher, by accepting the article for publication, acknowledges that the US Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).