Application of a systems approach to study the interactions of physiological state and nutrition on tissue function in livestock species is a powerful means to gain a holistic view of the underlying biological phenomena. Potential practical applications from applying such an approach in studies of mammary, adipose, and liver of dairy cows have emerged. In this chapter we present examples of studies encompassing changes across physiological state and level of dietary energy prepartum, an investigation of crosstalk between parenchyma and fat pad in developing bovine mammary gland, and dietary lipid supplementation effects on milk fat synthesis. Biological context of the data was uncovered through enrichment analysis of microarray data using a novel approach in combination with gene network and transcription factor motif analyses. The systems biology approach allowed visualization of the complexity of the systems at study and uncovered the main molecular players involved in the tissue's adaptations to physiological state or nutrition.