Nearly all licensed vaccines have been developed to confer protection against infectious diseases by stimulating the production of antibodies by B cells, but the nature of a successful antibody response has been difficult to capture. Recent advances in next-generation sequencing (NGS) technology have allowed high-resolution characterization of the antibody repertoire, and of the changes that occur following vaccination. These approaches have yielded important insights into the B cell response, and have raised the possibility of using specific antibody sequences as measures of vaccine immunogenicity. Here, we review recent findings based on antibody repertoire sequencing, and discuss potential applications of these new technologies and of the analyses of the increasing volume of antibody sequence data in the context of vaccine development. © 2014 Elsevier Ltd.