In this Leading article, we summarize current knowledge of the occurrence of the first and so far only transferable colistin resistance gene, mcr-1. Its location on a conjugative plasmid is likely to have driven its spread into a range of enteric bacteria in humans and animals. Screening studies have identified mcr-1 in five of the seven continents and retrospective studies in China have identified this gene in Escherichia coli originally isolated in the 1980s, while the first European isolate dates back to 2005. Based on the widespread use of colistin in pigs and poultry in several countries and the higher number of mcr-1-carrying isolates of animal origin than of human origin, it is tempting to assume that this resistance may have emerged in the animal sector. Whatever its origin, interventions to reduce its further spread will require an integrated global one-health approach, comprising robust antibiotic stewardship to reduce unnecessary colistin use, improved infection prevention, and control and surveillance of colistin usage and resistance in both veterinary and human medicine.