Antibodies are critical entities used for the protection of an individual organism against infection and disease. Through a complex series of events genes rearrange to encode repertoires of molecules, which are tested for their ability to identify foreign molecules. In this report, we discuss factors defined by the individual as well as by infectious organisms that shape the antibody repertoire. A more thorough understanding of the interplay between these factors will eventually allow us to elucidate the underlying mechanisms of disease susceptibility following infection, and to design potent vaccines and other immunomodulating reagents.