We are locked in an arms race with a diverse army of opponents capable of evolving much faster than we are. According to World Health Organisation estimates, infectious microbes are responsible for one in four deaths worldwide. This begs the question: how do infectious microorganisms adapt to live and cause disease in their hosts, and what factors influence this arms race? We are exploiting experimental evolution to investigate pathogen adaptation using the bacterium Citrobacter rodentium with its natural host (the laboratory mouse). This model system has direct relevance to human health as C. rodentium uses the same ‘modus operandi’ as some life-threatening human Escherichia coli strains. C57BL/6 mice were orally inoculated with the bioluminescent C. rodentium derivative ICC180 and individually housed animals allowed to infect naïve animals through tightly controlled mouse-to-mouse exposure, a process which was repeated weekly over a period of 6 months. Infection dynamics were followed using non-invasive real-time biophotonic imaging to identify any novel niches invaded by ‘evolving’ C. rodentium. Bacterial shedding in stools was monitored and stool and other host samples cryogenically stored each week. Despite C. rodentium’s competence as a pathogen, some “transmission failure” events were experienced, which may indicate reductions in transmissibility perhaps due to the bottlenecks inherent at each transmission step. We have identified the evolution of a hypertransmissible isolate and are currently working to identify phenotypic and genotypic changes in this ‘evolved’ C. rodentium. This work extends current flask-based experimental evolution with an evolution model which focuses on complex, medically relevant real-world environments.