Clostridium difficile is a unique pathogen that often predominates in the bowel microflora as a result of the microbial compositional changes following antibiotic treatment. The hospital environment and patients undergoing antibiotic treatment provide a discrete ecosystem where C. difficile persists and where virulent clones thrive. The continued rise of C. difficile infection (CDI) worldwide has been accompanied by the rapid emergence and transcontinental spread of highly virulent clones, designated PCR-ribotypes 017, 027 and 078. These strains have risen from obscurity to become the most frequently isolated C. difficile strain types. Additionally, patients infected with these strains often experience more severe diarrhoea, more recurrent episodes and higher mortality. Although C. difficile appears to be evolving to occupy the hospital niche, community acquired CDI is also on the increase: equally changes in human activity are likely to be responsible for creating the microenvironment for C. difficile to thrive. The rapid worldwide spread of the 017, 027 and 078 clones of C. difficile provides a valuable opportunity to study the very recent emergence of a bacterial pathogen-a rare chance to monitor evolution in action.