Functional proteomics is a promising technique for the rational identification of novel therapeutic targets and biological markers. The studies of protein-protein interactions have been gained from the development of high-throughput technologies such as the yeast two-hybrid system, protein arrays, phage display, and systematic analysis of interaction maps for the prediction of protein functions. Because antibodies are used extensively as diagnostic and clinical tools, the characterization of their antigen specificity is of prime importance. Indeed, screening protein arrays with sera from patients with either cancer or autoimmune diseases would facilitate the identification of autoantibody signatures that can be used for diagnosis and/or prognosis of patients. The usefulness of multiplexed measurements lies not only in the ability to screen many individual marker candidates but also in evaluating the use of multiple markers in combination. Here, we review the advantage of protein and serum screening of peptides and cDNA repertoires displayed on phages as well as the fabrication of protein microarrays for probing immune responses in patients.