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Clostridioides difficile infection (CDI) represents a significant challenge owing to its increasing incidence, severity, and treatment difficulty. Effective management requires a multifactorial approach that includes preventive strategies, prudent antibiotic use, and adapted therapeutic options. Ongoing research and innovation offer promising prospects for improving CDI management, making vigilance and informed practices essential among health-care professionals. Two main complications of CDI are pseudomembranous colitis (PMC) and toxic megacolon. PMC involves severe colonic inflammation due to C. difficile toxins, leading to pseudomembrane formation. Diagnosis relies on clinical criteria, microbiological tests, and endoscopy. Toxic megacolon is characterized by severe colonic dilation and systemic toxicity, requiring immediate medical intervention. CDI diagnosis combines clinical signs and microbiological tests. These tests include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture. Imaging techniques assess colonic inflammation and complications. Combined diagnostic criteria from the American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis. CDI treatment involves stopping the implicated antibiotics and starting specific antimicrobial therapy. Common treatments include fidaxomicin and oral vancomycin. Fecal microbiota transplantation (TMF) is recommended for recurrent cases that have been unresponsive to standard treatments. Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults. CDI poses a major challenge due to its increasing incidence, severity, and difficulty to treat. A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling the infection. Ongoing research and innovations in treatment offer promising prospects for improving patient management. Health-care professionals must remain vigilant and informed to ensure effective practices in combating this infection and to optimize the use of available resources.