Blood plasma is a complex body fluid that contains various proteins and small molecules including peptides, salts, lipids, amino acids and sugars. Plasma proteins perform different kinds of housekeeping functions, such as immunoresponse, coagulation, anticoagulation, transportation, nutrition and regulating signaling cascades, which normally are altered both in structure and amount during pathogenesis. These characteristics of plasma proteome are critical for disease diagnosis and therapeutic monitoring. Nevertheless, only a handful of proteins are currently well known and used in routine clinical diagnosis. A comprehensive, systematic characterization of circulating proteins and peptides in health and disease will greatly facilitate development of biomarkers for many human diseases. The human proteome organization has launched the Human Plasma Proteome Project as one of the major initiatives since April 2002. In the pilot phase of the project, as a “pathfinder” of human proteomics study, the major goals are (1) to compare the advantages and limitations of many technology platforms; (2) to compare reference specimens of human plasma (EDTA, heparin, citrate-anti-coagulated) and serum prepared specifically for this project with the technology platforms; and (3) to create a knowledge base. The brief introduction about the plasma proteome project including research status, major problems faced and technical strategies been used are reviewed.