Due to the lack of new antibiotics for the treatment of critically ill patients with multidrug-resistant bacteria, interest on "old" antibiotics like colistin (polymyxin E) re-emerged. This polymyxin has gained an important role as salvage therapy for patients infected with microorganisms susceptible only to colistin. It is important to know the dark face of colistin referring here to its important toxicity, often lethal, especially in critically ill patients. Given its rarity we briefly mentioned a case of profound encephalopathy in a post-surgical patient who recovered completely after stopping the drug. In addition, its variable pharmacokinetics make it very difficult to establish an effective regimen, most of which is infratherapeutic and with the limitation of its toxicity, which is a terrible problem for humanity. The common sense of the clinician and the birth of new antibiotics, as an alternative strategy, represent a hope to eradicate multiresistance.