A new era of quantitative biology enabled by mass spectrometry-based proteomic technologies has arrived. We can now define the content, relative abundance, modification states and interaction partners of proteins in a dynamic and temporal manner on a near-global basis in organelles, whole cells and clinical samples, providing information of unprecedented detail. At the Broad Institute we are developing and applying and automating these technologies in a wide array of studies to connect cancer genotype to molecular phenotype, quantitatively profile changes in the post-translational modification landscape in health and disease, and to identify the mechanism of action of drugs molecules and understand the bases of response and resistance to therapy. We will provide a high-level overview of proteomics at the Broad and present the results of several recent studies that convey a sense of the breadth and depth of application of modern quantitative proteomics to biology and medicine.