Colistin is currently regarded as one of the 'last-resort' antibiotics used for the treatment of critical infections caused by multidrug-resistant Gram-negative pathogens. There have been numerous reports of the emergence of colistin resistance in patients, most of whom had previously received colistin therapy or with acquisition via nosocomial transmission. However, there are also ample reports of colistin resistance in humans who have not received the drug previously or without nosocomial transmission. We have also observed a similar occurrence in our study involving colistin resistance from several countries along with a similar phenomenon being reported by researchers. The observation of colistin resistance in humans without prior colistin exposure is of particularly great clinical importance and concern because of the current importance of colistin in clinical medicine. Colistin use and colistin-resistant bacteria in animals have been recently reported, suggesting that animals could also be a source of transmission of colistin- resistant bacteria to humans. This is a real worry and calls for clinicians to be aware and vigilant of this phenomenon and of the possibility of independent resistance to colistin in some patients.