Elucidation of the cellular and molecular mechanisms which determine the expressed antibody repertoire remains a major challenge in immunology. Knowledge of V gene diversity, organization, and expression is important to an understanding of the formation of the antibody repertoire in normal as well as diseased states. In the last few years, great advances have been made in our understanding of the human heavy chain variable region (VH) gene locus. In this review we present the current knowledge of VHgene diversity, organization, and utilization in normal individuals followed by a discussion of the possible relevance of these findings to autoimmunity.