All this variability evolved to make immunoglobulin variable domains predestined to quickly optimize binding sites for the various types of antigens. Current efforts to mimic this evolution of antibody producing cells in response to the stimulus of an infection or immunization by in vitro methods such as randomization and selection of natural or synthetic antibody libraries by phage panning, selective infective phage and ribosome display techniques can profit from a thorough analysis of how antibodies recognize antigens.