The energetic, physiological or metabolic efficiency of an animal depends on various factors, including the ingredients and physical form of the animal’s diet; the bacterial population in their digestive tract; and the interactions between their hormones, receptors, organs and metabolism patterns. In this chapter, we give a brief review of the physiology and biochemistry of the cow, and then offer an overview of the development of the biology of lactation as a research field, with particular emphasis on the growing role of genetics. Section 4 then discusses a case study on the biochemical determinants of feed efficiency in dairy cows, and finally Section 5 explores the effects of genetic variation on metabolism.