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<i>Clostridioides difficile</i> remains an important public health threat, globally. Since the emergence of the hypervirulent strain, ribotype 027, new strains have been reported to cause <i>C. difficile</i> infection (CDI) with poor health outcomes, including ribotypes 014/020, 017, 056, 106, and 078/126. These strains differ in their geographic distribution, genetic makeup, virulence factors, and antimicrobial susceptibility profiles, which can affect their ability to cause disease and respond to treatment. As such, understanding <i>C. difficile</i> epidemiology is increasingly important to allow for effective prevention measures. Despite the heightened epidemiological surveillance of <i>C. difficile</i> over the past two decades, it remains challenging to accurately estimate the burden and international epidemiological trends given the lack of concerted global effort for surveillance, especially in low- and middle-income countries. This review summarizes the changing epidemiology of <i>C. difficile</i> based on available data within the last decade, highlights the pertinent ribotypes from a global perspective, and discusses evolving treatments for CDI.