The NIH Roadmap Epigenomics Program was launched to deliver reference epigenomic data from human tissues and cells, develop tools and methods for analyzing the epigenome, discover novel epigenetic marks, develop methods to manipulate the epigenome, and determine epigenetic contributions to diverse human diseases. Here, we comment on the outcomes from this program: the scientific contributions made possible by a consortium approach and the challenges, benefits, and lessons learned from this group science effort.