The success of the human genome sequencing project has created wide-spread interest in exploring the human epigenome in order to elucidate how the genome executes the information it holds. Although all (nucleated) human cells effectively contain the same genome, they contain very different epigenomes depending upon cell type, developmental stage, sex, age and various other parameters. This complexity makes it intrinsically difficult to precisely define 'an' epigenome, let alone 'the' epigenome. What is clear, however, is that in order to unravel any epigenome, existing and novel high-throughput approaches on the DNA, RNA and protein levels need to be harnessed and integrated. Here, we review the current thinking and progress on how to get from the genome to the epigenome(s) and discuss some potential applications.