Over the past decade, it has become a cliché that the deep sequencer is the microscope for modern chromatin researchers. Like many clichés, this analogy has some truth to it, as epigenomics methods provide a view of ensemble chromosome organization that approaches atomic resolution in some respects. Although heterogeneity in cell populations will always remain a significant confounding factor, it is clear that epigenomic assays of stringently selected cell populations will continue to provide structural insights into the folding of the chromosome, while single-cell methods have the promise to rigorously disentangle inevitable heterogeneity between individual cells. The coming decade promises continuing insights into the structure of eukaryotic genomes, and we anticipate that further investigations will continue to reveal the mechanistic principles responsible for chromosome folding and the functional importance of chromosomal substructures.