Most proteins do not exist as isolated molecules in the cell, but instead serve as nodes of protein interaction networks. A number of techniques have been developed in the last two decades to study protein interaction networks at different levels of detail. Here we describe some of the techniques for characterizing protein interactions and protein complexes on a system-wide scale, focusing especially on newly emerging techniques that use co-migration. These newer approaches have the advantage that no genetic manipulation is necessary, thereby allowing investigation of protein complexes at their endogenous levels in the correct cellular context. Finally, we discuss different approaches for measuring large-scale temporal changes to protein interaction networks, an area that we believe will be one of the frontiers in systems biology in the coming years.