The 3rd Annual DREAM (Dialogue for Reverse Engineering Assessments and Methods) Conference was held at the Broad Institute in Boston from October 29th to November 2nd 2008, jointly with the 5th Annual RECOMB Satellite Conference on Regulatory Genomics and the 4th Annual RECOMB Satellite Conference on Systems Biology. The meeting was organized by the Broad Institute of MIT and Harvard, and the MIT Computer Science and Artificial Intelligence Lab (CSAIL). The meeting brought together computational and experimental scientists in the area of regulatory genomics, to discuss current research directions, latest findings, and establish new collaborations towards a systems-level understanding of gene regulation. The program comprised 16 keynote presentations, 93 oral presentations selected from submitted manuscripts and 1-page abstracts, and 160 posters in four poster sessions. More than 500 participants registered attended the joint meeting, of which the vast majority attended all three meetings. Conference Chairs: Manolis Kellis (MIT), Andrea Califano Columbia University, Gustavo Stolovitzky (IBM). Organizing Commitee: Eleazar Eskin, Nir Friedman, Leroy Hood, Trey Ideker, Douglas Lauffenburger, Satoru Miyano, Eran Segal, Ron Shamir. Partner journal editors: Hillary Sussman, CSHL (Genome Research), Thomas Lemberger, EMBO (Nature MSB), Sorin Istrail, Brown University (Journal of Computational Biology).