Systematic genome-wide and pathway-specific protein-protein interaction screens have generated a putative, organizing framework of the spatial interconnectivity of a large number of human proteins, including numerous therapeutically relevant disease-associated proteins. The intrinsic value for drug discovery is that these physical protein-protein interaction networks may contribute to a mechanistic understanding of the pathophysiology of disease and can aid in the identification and prioritization of tractable targets and generate hypotheses on how to best drug non-tractable, disease-associated targets. Here, we review the 'therapeutic potential' of the 1st generation sub-genome-scale human interaction networks and disease-associated protein networks generated by yeast two-hybrid screens and affinity purification-mass spectrometry approaches.