The generation of new drugs has long involved the screening of hundreds of thousands of components with well defined in vitro tests, seeking compounds to mimic as closely as possible the desired in vivo activity of the new drug. New library methodologies offer many alternative routes that are at least as powerful as traditional approaches by combining the generation of billions of components with a fast screening or selection procedure to identify the most interesting lead candidates. One of the most widely used library methodologies is based on the use of filamentous phage (1 ), a virus that lives on Escherichia coli. Phage display has proven to be a powerful technique for the interrogation of libraries containing millions or even billions of different peptides or proteins. One of the most successful applications of phage display has been the isolation of monoclonal antibodies using large phage antibody libraries (2 ,3 ). This chapter reviews the progress made in this rapidly developing field and discusses a broad range of applications, including the use of large phage Ab libraries to discover novel therapeutic targets and methods for selection of biologically active ligands. Finally, it addresses the potential of combining phage display with complementary methods to increase the scope and range of applications of this technology.