Clostridium difficile-associated disease (CDAD) is caused by a spore-forming bacterium and can result in highly variable disease, ranging from mild diarrhoea to severe clinical manifestations. Infections are most commonly seen in hospital settings and are often associated with on-going antibiotic therapy. Incidences of CDAD have shown a sustained increase worldwide over the last ten years and a hypervirulent C. difficile strain, PCR ribotype 027/REA type BI/North American pulsed-field (NAP) type 1 (027/BI/NAP-1), has caused outbreaks in North America and Europe. In contrast, only a few reports of cases in Latin America have been published and the hypervirulent strain 027/BI/NAP-1 has, so far, only been reported in Costa Rica. The potential worldwide spread of this infection calls for epidemiological studies to characterize currently circulating strains and also highlights the need for increased awareness and vigilance among healthcare professionals in currently unaffected areas, such as Latin America. This review attempts to summarize reports of C. difficile infection worldwide, especially in Latin America, and aims to provide an introduction to the problems associated with this pathogen for those countries that might face outbreaks of epidemic strains of C. difficile for the first time in the near future.