The analysis of protein-protein interactions is important for developing a better understanding of the functional annotations of proteins that are involved in various biochemical reactions in vivo. The discovery that a protein with an unknown function binds to a protein with a known function could provide a significant clue to the cellular pathway concerning the unknown protein. Therefore, information on protein-protein interactions obtained by the comprehensive analysis of all gene products is available for the construction of interactive networks consisting of individual protein-protein interactions, which, in turn, permit elaborate biological phenomena to be understood. Systems for detecting protein-protein interactions in vitro and in vivo have been developed, and have been modified to compensate for limitations. Using these novel approaches, comprehensive and reliable information on protein-protein interactions can be determined. Systems that permit this to be achieved are described in this review.