Proteins very rarely act in isolation. Biomolecular interactions are central to all biological functions. In human, for example, interference with biomolecular networks often lead to disease. Protein-protein and protein-metabolite interactions have traditionally been studied one by one. Recently, significant progresses have been made in adapting suitable tools for the global analysis of biomolecular interactions. Here we review this suite of powerful technologies that enable an exponentially growing number of large-scale interaction datasets. These new technologies have already contributed to a more comprehensive cartography of several pathways relevant to human pathologies, offering a broader choice for therapeutic targets. Genome-wide scale analyses in model organisms reveal general organizational principles of eukaryotic proteomes. We also review the biochemical approaches that have been used in the past on a smaller scale for the quantification of the binding constant and the thermodynamics parameters governing biomolecular interaction. The adaptation of these technologies to the large-scale measurement of biomolecular interactions in (semi-)quantitative terms represents an important challenge.