Abstract Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid species bound to nucleoproteins of the genome. In vitro, some of these lipid species exhibit stoichiometric association with DNA polynucleotides with differential affinities toward certain secondary and tertiary structures. Hydrophobic interactions with inner nuclear membrane could provide attractive anchor points for lipid-modified nucleoproteins in organizing the dynamic genome and accordingly there are precedents for covalent bonds between lipids and core histones and, under certain conditions, even DNA. Advances in biophysics, functional genomics, and proteomics in recent years brought about the first sparks of light that promises to uncover some coherent new level of the epigenetic code governed by certain types of lipid–lipid, DNA–lipid, and DNA-protein–lipid interactions among other biochemical lipid transactions in the nucleus. Here, we review some of the older and more recent findings and speculate on how critical nuclear lipid transactions are for individual cells, tissues, and organisms.