Understanding the interactions between metabolites and small molecules on one hand, and the proteome on the other, are vital for our understanding of biological phenotypes, metabolism and drug action. In this lecture, I’ll summarize our efforts in developing methods for high-throughput proteomics. I’ll further show examples that illustrate how high-throughput proteomic datasets allow to bridge genome, proteome and metabolome. The results indicate that genome-scale proteomic data opens new avenues for understanding gene function and interactions within biological systems, could impact drug discovery, and lead to a new generation of diagnostic and prognostic tests in medicine.