This article provides a comprehensive overview of *Clostridium difficile* infection (CDI), a potentially life-threatening condition, particularly in elderly patients and those with gut microbiome dysbiosis following antimicrobial exposure. *C. difficile* is the leading cause of healthcare-associated diarrhea. The lifecycle of *C. difficile* is influenced by host microbiota, associated metabolites, antimicrobial agents, and the immune system. The primary mediators of inflammation in CDI are the large clostridial toxins, Toxin A (TcdA) and Toxin B (TcdB), and the binary toxin CDT in some strains. These toxins trigger a complex cascade of host cellular responses, leading to diarrhea, inflammation, and tissue necrosis. The factors responsible for the epidemic of certain *C. difficile* strains are not fully understood, and recurrent infections are common. Toxin detection is crucial for accurate epidemiological studies and optimal management and prevention strategies. Treatment options include specific antimicrobial agents and fecal microbiota transplants, with future biotherapies likely involving defined combinations of key gut microbiota. The article also discusses the epidemiology, mechanisms of pathogenesis, experimental models, diagnosis, screening, prevention, and management of CDI, including infection control measures and antimicrobial therapy.This article provides a comprehensive overview of *Clostridium difficile* infection (CDI), a potentially life-threatening condition, particularly in elderly patients and those with gut microbiome dysbiosis following antimicrobial exposure. *C. difficile* is the leading cause of healthcare-associated diarrhea. The lifecycle of *C. difficile* is influenced by host microbiota, associated metabolites, antimicrobial agents, and the immune system. The primary mediators of inflammation in CDI are the large clostridial toxins, Toxin A (TcdA) and Toxin B (TcdB), and the binary toxin CDT in some strains. These toxins trigger a complex cascade of host cellular responses, leading to diarrhea, inflammation, and tissue necrosis. The factors responsible for the epidemic of certain *C. difficile* strains are not fully understood, and recurrent infections are common. Toxin detection is crucial for accurate epidemiological studies and optimal management and prevention strategies. Treatment options include specific antimicrobial agents and fecal microbiota transplants, with future biotherapies likely involving defined combinations of key gut microbiota. The article also discusses the epidemiology, mechanisms of pathogenesis, experimental models, diagnosis, screening, prevention, and management of CDI, including infection control measures and antimicrobial therapy.