The aim of this project is to improve our understanding of the role of recombination (uptake and incorporation of foreign DNA) for the evolution and epidemiology of the major human bacterial pathogen Streptococcus pneumoniae, also known as the pneumococcus. There is an increasing appreciation of the public health significance of recombination in S. pneumoniae, where recombination has enabled major drug-resistant lineages to rapidly evade new conjugate vaccines. Here, I propose to investigate the role of different mechanisms of recombination in the context of (a) coevolution of the pathogen with the human immune system, (b) generation of novel antigenic diversity at the capsular locus, and (c) adaptation to clinical treatment by generation of novel bacterial lineages carrying multi-drug resistant genes and vaccine “escape” antigens. To do so, I will use an interdisciplinary approach of evolutionary microbiology, immunology, and epidemiology of infectious diseases. First, I will employ a generic evolutionary-epidemiological modelling approach to understand the population dynamic of recombination. Second, I will analyse newly available pneumococcal full-genome sequences to examine the link between recombination, immunity, vaccine, and drug-resistance in pneumococcus. The benefit of this research will be threefold. First, a better understanding of the role of recombination in coevolution with the human populations would be of benefit to the field of bacterial evolution and microbiology in general. Second, the approach outlined here can be applied to study recombination in other recombinogenic bacterial pathogens, like Neisseria meningitidis, Salmonella enterica or Helicobacter pylori. Finally, gaining further insight into the predicted long-term response against the current and future vaccines would help in the design of more effective forms of clinical interventions and help saving children’ lives.