ENCODE, the Encyclopaedia of DNA Elements, is the most ambitious human genetics project to date. It takes the 3 billion letters described by the Human Genome Project in 2000, and tries to explain them. Remarkably, ENCODE scientists have managed to assign a biochemical function to 80% of the genome, including the genes and the parts of the genome that tell those genes what to do. This information is helping us understand how genomes are interpreted to make different types of cells and different people -- and crucially, how mistakes can lead to disease. In this video, ENCODE's lead coordinator, Ewan Birney, and Nature editor Magdalena Skipper talk about the challenges of managing this colossal project and what we've learnt about our genomes.