Over the past twenty years diverse groups in Northeast Asia, Western Europe, and North America have competed to map, sequence, and characterize the immunoglobulin loci of mouse and man. Now that this work is near completion, it has become evident that the human and mouse germline repertoires share broad similarities in gene composition, organization, and other general principles. In spite of these similarities, the repertoires expressed by adult mice and humans are distinct and differ from each other in detail. In both species the mechanisms used to create repertoire diversity appear designed to generate a random range of antigen binding sites. However, a detailed analysis reveals significant constraints in the sequence and amino acid composition of the third complementarity region of the H chain (CDR-H3), which lies at the center of the antigen binding site. The mechanisms used to regulate the composition of the repertoire, their significance to the development and maintenance of immune competence, and the contribution of violation of normal repertoire boundaries to the development of diseases of immune function remain foci of ongoing investigation. © 2005 Elsevier Ltd. All rights reserved.