Protein-protein interactions are crucial for a wide variety of biological processes. These interactions range from high affinity (K (d)<nM) to very low affinity (K (d)>mM). While much is known about the nature of high affinity protein complexes, our knowledge about structural characteristics of weak protein-protein interactions (wPPIs) remains limited: in addition to the technical difficulties associated with their investigation, historically wPPIs used to be considered physiologically irrelevant. However, emerging evidence suggests that wPPIs, either in the form of intact protein complexes or as part of large molecular machineries, are fundamentally important for promoting rapid on/off switches of signal transduction, reversible cell-cell contacts, transient assembly/disassembly of signaling complexes, and enzyme-substrate recognition. Therefore an atomic-level elucidation of wPPIs is vital to understanding a cornucopia of diverse cellular events. Nuclear magnetic resonance (NMR) is famous for its unique abilities to study wPPIs and, by utilization of the new technical developments combined with sparse data based computational analysis, it now allows rapid identification and structural characterization of wPPIs. Here we present our perspective on the NMR methods employed.