Large-scale genomic data have been utilized to generate unprecedented biological findings and new hypotheses. To delineate functional elements in the human genome, the Encyclopedia of DNA Elements (ENCODE) project has generated an enormous amount of genomic data, yielding around 7,000 data profiles in different cell and tissue types. In this article, we reviewed the systematic analyses that have integrated ENCODE data with other data sources to reveal new biological insights, ranging from human genome annotation to the identification of new candidate drugs. These analyses demonstrate the critical impact of ENCODE data on basic biology and translational research.