Advances in high throughput biology have revolutionized the study of milk and mammary gland biology. This talk will review applications of genomics, epigenetics, transcriptomics, proteomics, and metagenomics in the field. The availability of mammalian genome sequences, particularly the bovine genome assembly, enabled multi-species comparisons of the genes that are expressed to produce milk. Across mammals, gene duplication and protein sequence variation both contributed to differences in milk composition. ChIP-Seq and transcriptomic data were then leveraged to understand epigenome-wide features involved in milk production. Identification of cis-regulatory elements in the bovine genome using RNA-Seq and ATAC-Seq technology is ongoing. Meanwhile, non-invasive technologies to study mammary biology in humans using RNA-Seq of milk fat RNA have been developed and validated. Whole transcriptome comparisons in a non-human primate model demonstrated that RNA from milk samples provides a more accurate representation of RNA from milk-producing cells than does RNA from whole mammary tissue. Advances in proteomics have expanded the milk proteome from dozens to thousands of unique proteins. The use of RNA-Seq to develop a comprehensive database of protein sequences has the potential to further expand the milk proteome to include isoforms of milk proteins. Finally, microbial metagenomics can be used to survey all microbes in a sample to investigate causal agents in mastitis, manage spoilage organisms, or track antibiotic resistance. Applications of these “omic” technologies in dairy science will be discussed.