This volume contains a selection of chapters based on papers presented at the Fourth Seattle Symposium on Biostatistics: Clinical Trials. These biostatistical symposiums, which unite leading researchers every five years, represent important developments in field. The Fourth Seattle Symposium was held in 2010 to celebrate the 40th anniversary of the University of Washington School of Public Health and Community Medicine. The Symposium featured keynote lectures by Robert O’Neill, Ross Prentice and Robert Temple, as well as invited talks by Jesse Berlin, Christy Chuang-Stein, David DeMets, Bill DuMouchel, Susan Ellenberg, Thomas Fleming, Laurence Freedman, Margaret Pepe, Steve Self, Richard Simon, Bruce Weir, John Whittaker and Janet Wittes.  Invited panelists included Jesse Berlin, Bruce Binkowitz, Christy Chuang-Stein, Bill DuMouchel, Susan Ellenberg, Thomas Fleming, Henry Fuchs, Dominic Labriola, Robert O’Neill, Robert Temple and Janet Wittes. The thoroughly peer-reviewed papers and material from short courses that are showcased in this volume represent the theme of the symposium, clinical trials. These papers encompass recent methodological advances on several important topics, summaries of the state of the art of methodology in key areas of clinical trials, as well as innovative applications of the existing theory and methods. This volume will be a valuable reference for researchers and practitioners in the field of clinical trials.