While it sometimes does not generate the publicity that biomarker discovery does, the identification of protein complexes may be the most popular use of proteomic technology. The partners a protein interacts with is a key component that describes the function of any protein. Basic research has long appreciated the importance of identifying protein interactions through techniques such as Western blotting and colocalization studies using immunofluorescence microscopy. This appreciation has carried over into the field of proteomics and brought with it the development of tools that increase the capabilities to characterize protein complexes to a far greater scale. While advances in technology have had a huge impact, sample preparation issues related to the isolation of protein complexes remains a critical factor in determining the success of these types of studies.