Clostridioides difficile is a gram-positive anaerobic bacterium that is the most common cause of infectious diarrhea. The incidence and mortality rate of C. difficile infection have increased significantly in hospital and community settings over the past two decades. The increase in infection can be caused by multiple factors including inappropriate use of antibiotics, poor standards of cleanliness of the patient environment, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, changes in circulating strains of C. difficile and the spread of hypervirulence. The clinical picture of the disease varies in severity from from mild diarrhea to fulminant colitis and death. Appropriate treatment of infection requires an understanding of the various diagnostic tests and therapeutic options, as well as relevant infection prevention measures. Treatment of C. difficile infection involves an approach that includes discontinuing the antibiotics that are causing the infection, isolating the patient, and using antibiotics depending on the severity of the infection. Prevention of the occurrence and spread and treatment of C. difficile infection in healthcare institutions requires a coordinated approach by all members of the healthcare team. The foundations of these efforts are the reduction of prolonged use of multiple antibiotics and the prevention of patient-to-patient transmission. Nurses/technicians have the most important role in preventing the spread of infection because they are the first in contact with the patient and have the opportunity to educate the patient and other medical and non-medical personnel. Hand hygiene is a key procedure recommended to prevent and control the transmission of pathogens within healthcare settings to ensure that patients remain safe and that their risks of contracting a particular infection are minimized.