Population genetics of Bordetella pertussis has long wrestled with a conflicting dichotomy of low gene sequence variation and high restriction fragment profile diversity. Recent applications of high-throughput sequencing and bioinformatics have deepened understanding of Bordetella evolution confirming that frequent chromosome rearrangement is a significant source of diversity in this species, in addition to gradual modification of protein-coding gene sequences. This chapter summarizes recent progress in the study of B. pertussis genomics to characterize temporal genetic shifts in the circulating population. Much of the presented work reinforces the dichotomy of B. pertussis genome evolution, concurrent mutation both of nucleotide sequences and gene arrangements, which still presents challenges in the genomic era. Disentangling the specific contributions of these processes to disease resurgence, as well as exploring their potential utility for vaccine development and novel therapeutics, provides a wealth of future research opportunities.