Clostridium difficile, recently renamed to Clostridioides difficile is the main cause of nosocomial diarrhea in developed nations. In recent years the appearance of so called “hypervirulent” strains like ribotype 027 (RT027) originating from North America has shaped the epidemiology in many parts of the world posing a huge burden on the healthcare system. These hypervirulent strains among others (e. g. RT017) are associated with resistance towards several antibiotics (e. g. fluoroquinolones) favoring their selection. In Europe, Israel and the American continent RT027 seems to have become the most prevalent strain, while in other parts of the world other RTs dominate. In Far East Asia, RT017 is the predominant strain, while in Australia RT014/020 and RT002 are mostly prevalent. However, for most parts of the world the C. difficile world map is rather incomplete, such as in most African countries, Middle East Asia, South Asia but also Eastern Europe including the Russian Federation. Multi-center studies are therefore needed to assess the impact of this pathogen including its molecular epidemiology and corresponding resistance.