As the methods for high resolution analysis of proteins and their complexes become of age, a systems-level approach is now needed to understand molecular organization in each cell type, from a skin cell to a neuron, in healthy conditions and in disease. This next critical step in our understanding of the cell requires development of approaches to obtain quantitative data of every component of the protein complex at the single cell level, in combination with its location within the cell. These challenges set the stage for future molecular cell biological analysis and provide opportunities for high precision therapeutic intervention in multiple disease areas.