Mammalian lipoproteins are synthesized in the liver and secreted into the blood plasma where they are targeted to specific tissues. Through specific cell surface receptors, hepatic lipoproteins are taken up and their lipid contents are then used for anabolic and energy requirements. Because of the well-established role that plasma lipoproteins play as risk factors for the development of cardiovascular disease, a great amount of attention has been directed toward understanding their metabolism and biosynthesis. The major focus of this report is to review the evolution of gene products that are essential in regulating, synthesizing, assembling and secreting the lipid and protein components of lipoproteins. Using the primordial vitellogenin lipoprotein system as the paradigm, I show how metabolic signals derived from the sterol biosynthetic pathway provide a coordinate regulation of genes necessary to assemble and secrete mammalian apolipoprotein B-containing lipoproteins. In lower species, estrogen induces the expression of genes required for both vitellogenin synthesis and its tissue targeting (the vitellogenin receptor). This coordinate induction provides lipid to the ovaries for egg development. In mammals, a sterol-derived metabolic signal regulates the expression of genes required for lipoprotein synthesis and for the LDL receptor. The signal is not sex linked, providing an adaptive advantage to changes in nutritional status.