Implant infection remains the major and often irreducible complication in clinical use of biomaterials, demanding new therapeutic and preventive strategies. Etio-pathogenesis of biomaterials-related infections is being more and more studied, and various virulence bacterial factors have progressively been identified, but little is still known about the weight of the distinct molecules in the context of specific peri-implant infection sites. Molecular epidemiology has become recently integrated into the research on implant infections. What distinguishes molecular epidemiology from the simple molecular biology is that the use of molecular techniques is applied to the study of the distribution and prevalence of virulence and resistance genes in collections of bacterial clinical isolates from implant infections. Here, the authors comment on the range of molecular techniques available, reviewing the various applications of molecular epidemiology to the study of implant infections and providing some experimental examples related to the field of orthopaedic implant infections. They highlight the new opportunities arising from molecular epidemiology of designing measures useful to prevent and treat implant infections. The knowledge of the relative weight of virulence factors and of their regulatory mechanisms at molecular level can open the way to new strategies also including gene therapies aimed at silencing or knocking out crucial genes responsible for the aggressive tools (adhesins, biofilm production, antibiotic resistance) of the aetiological agents of implant-related infections.