Abstract: Research over the past decade have revealed that a fairly large set of protein are accomplished by peptide-binding domains that recognize short peptide motifs in their binding partners, such as SH2，WW，SH3，etc. Protein interaction domains play important roles in critical cellular functions, such as subcellular localization, signal transduction, and multiprotein complexes assembly. With the development of proteomics, high-throughput technology has been applied to explore binding properties and interaction networks of domains. In this review, several proteomic strategies for domain research were summarized with SH3 and WW domains as examples.