With the advent of post-genomic era, identification of protein-protein interaction has become another hot spot of protein research and promoted the invention, development and complement of relative techniques. Major large-scale high-throughput methods, such as two-hybrid system, bacteriophage display, mass spectrometry, protein microchips and bioinformatics have provided a global view of protein-protein interaction, and are hopeful to play an important role in proteomics. Each method may have its specific strengths and weaknesses as well as differences in coverage, to some extent, the data based on these methods can complete each other. Here, recent progress of these large-scale high-throughput methods and their applications for studying protein-protein interaction are reviewed.