Background: Clostridium difficile (CD) infection is widespread throughout the world, showing an increased incidence over the recent years and may cause severe forms of disease. This infection most commonly affects patients whom were administered antibiotics. An increased resistance to commonly used antibiotics is associated with Clostridium difficile infection (CDI). CD has a generally recognized infectious potential on a clinical ground. CDI is unpleasant and may sometimes cause serious bowel disorders that are usually treated with another course of antibiotics. The evolution of CD infection depends on the individual characteristics of the patient along with risk factors, associated diseases as well as the particularities of the recommended treatment. However, even under the conditions of a correct and complete treatment the risk of the disease relapse is estimated to occur depending on risk factors. Many clinical instruments that are designated for the purposes to treat non-infectious diseases can be useful in estimating the severity of an infection. This review is important for understanding the abusive and irrational prescription of various groups of antibiotics, often unjustified, including the ones used in the treatment of an infection with SARS-CoV-2. Conclusions: These infections mostly occur in people aged 65 and older that receive medical care, including antibiotics administration, people with a long-term hospital stay, people with a weakened immune system or with a previous CD infection. The following measures, in order to reduce the risk of CDI in patients, should be considered: hand hygiene, avoidance of unnecessary administration of antibiotics – the antibiotic treatment is recommended only if it is prescribed by an experienced specialist, avoidance of unnecessary administration of drugs that reduce gastric acidity, because it favors the invasion of the gastrointestinal tract with CD.