Clostridium difficile infection represents a severe illness which very often results in emergency surgery, intensive care unit stay or death. Although standard treatment procedures are well known and seem to be sufficient at the first glance, there is need for improvement of therapy guidelines due to high rates of recurrences or treatment failures. This article suggests some adjustments so far without claiming to be a complete review of all new development in this area. On the one hand, the recent actualization of the European guideline has been taken as a basis of this report; on the other hand some new highly promising developments in the treatment of CDI are exemplarily reported. Possibly the development with the highest impact in literature is fecal transplantation (or better said microbiome instillation). However, standard therapies need some critical review as well: an upgrading of vancomycin to first-line therapy and with a higher daily dose (250 mg qid) might be beneficial for many patients. For severe CDI, there is a recommendation against the usage of metronidazole, since vancomycin represents a better alternative. The dosage ofvancomycin might be further increased: although some authors are precautious in this point, dosage of vancomycin 500 mg qid should be favored. Last but not least, the pipeline bears some good tools for treatment of recurrent and complicated CDI, first data are promising and we hope for more.