Although vaccination has been effective, Bordetella pertussis is increasingly causing epidemics, especially in industrialized countries using acellular vaccines (aPs). One factor behind the increased circulation is the molecular changes on the pathogen level. After pertussis vaccinations were introduced, changes in the fimbrial (Fim) serotype of the circulating strains was observed. When bacterial typing methods improved, further changes between the vaccine and circulating strains, especially among the common virulence genes including pertussis toxin (PT) and pertactin (PRN) were noticed. Moreover, development of genome based techniques including pulsed-field gel electrophoresis (PFGE), multiple-locus variable number tandem repeat analysis (MLVA) and whole-genome sequencing (WGS) have offered a better resolution to monitor B. pertussis strains. After the introduction of aP vaccines, B. pertussis strains that are deficient to vaccine antigens, especially PRN, have appeared widely. On the other hand, antimicrobial resistance to first line drugs (macrolides) against B. pertussis is still low in many countries and therefore no globally evaluated antimicrobial susceptibility test values have been recommended. In this review, we focus on the molecular changes in the bacteria, which have or may have affected the past and current epidemiology of pertussis.