Research over the past few decades underscores that cellular and organ systems within the dairy cow interact in a coordinated fashion to regulate metabolism and immune function, all of which influence nutrient use efficiency. In this Special Issue, papers review the state of knowledge regarding essential nutrients, bioactive compounds, and key physiologic components that in concert help regulate dairy cattle function during various stages of the life cycle. Topics encompassed range from basic discovery research on how essential nutrients and novel bioactive compounds alter tissue function to applied principles and practical feeding approaches considering new knowledge of the biological components of feed efficiency. Journal of Animal Science and Biotechnology is a leading open access journal publishing innovative research across agriculture, dairy and animal science.