The nucleus is perhaps the defining feature of ‘eukaryotes’ (Greek ‘eu-’ (with) ‘-karyon’ (kernel, nucleus)), and the emperor of all eukaryotic organelles in terms of scale and complexity of organization. It is, of course, the repository for almost all genomic information, encoded in DNA sequences wrapped into chromatin as discrete polymer packages termed chromosomes, surrounded in turn by a double-membrane nuclear envelope (NE). Our investment in genomics in humans and other eukaryotes has been rightly huge; however, the return has been slow, as we discovered that sequence assemblies alone reveal little about how genetic information is utilized. Instead, genome functions are greatly influenced by processes that control nuclear and chromosome architecture and dynamics — chromatin factors and modifications, epigenetic mechanisms, and pathways for controlling transport of molecules into and out of the nucleus.