The bacterial genus Yersinia comprises species responsible for enteric infections, Y. pseudotuberculosis and Y. enterocolitica, as well as the plague bacillus Y. pestis. Besides our public health missions concerning diagnostics improvement and disease surveillance, we are interested in investigating diversity and virulence evolution in these pathogenic bacteria. Genomic analysis of our historical bacterial collections has brought novel perspectives on the global spread and molecular mechanisms driving the recent evolutionary trajectories of Y. pseudotuberculosis and Y. pestis. In parallel, collaborations with colleagues from the field of ancient DNA has allowed us to investigate the attenuation of Y. pestis virulence across three plague pandemics, as well as the impact of plague on the evolution of the human immune system. Our work has additionally implications for the development of novel plague vaccine based on an attenuated live Y. pseudotuberculosis strain.