Clostridium difficile infection has become one of the most significant threats to hospitalised patients and represents an increasingly important issue in terms of morbidity and mortality within our institutions. The arrival of a new, more virulent strain coincided with the introduction of several new respiratory fluoroquinolones, and several studies have reported a potential link between the use of fluoroquinolones and the occurrence of C. difficile infection. After reviewing the available published data on this topic the evidence for a link seems to be suggestive but not conclusive. Infection-control issues seem to play a more important role than fluoroquinolone use.