The challenges to food research are to propel foods beyond the successes of safety, convenience, and inclusion of all the essential nutrients, and to build the knowledge of genetics, metabolism, and biomolecules necessary for developing foods that deliver optimal health to each individual. How then can scientific and biological principles be developed to assemble this knowledge? The evolutionary success of milk has afforded compelling examples of a food material designed by selective pressure to provide optimal health to healthy mammalian offspring. Milk contains components that are more than assembled essential amino acids and that provide biological activities that improve the competitive success of offspring who consume them. Many of these molecules are proteins that protect individuals from exogenous stresses, toxins, and pathogens; encourage optimal growth, development, and adaptation to a chosen environment; and promote metabolic regulation for physical and intellectual performance. These structures and their actions are the basis of nutritional benefits that were not recognized when freedom from amino acid deficiency was the sole criterion of protein quality. The rapidly expanding tools of biotechnology are enabling a new perception of ingested proteins, how they are regulated, and how they achieve their specific functions. Genomes and their analyses are revealing the molecular details of their remarkable structural complexity and design. Milk proteins, either exclusively synthesized in the mammary gland during lactation or transported from plasma and concentrated in the mammary gland, have been largely co-opted from other functions. Establishing the evolutionary lineage of orthologous milk proteins, including the physiological process from which they were recruited, will lead to identification of their bioactivity. While most emphasis has been placed on the genes per se, our approaches implicate the regulatory regions of the genome as additional targets of milk's biological information content. Understanding the structures is guiding scientists to new food ingredients. Understanding structures and regulation will guide scientists to new benefits and ultimately to the knowledge to build a new generation of delicious foods that genuinely deliver on the promise of safety and maintenance of optimal health.