The proliferation of infections that can not be treated is a nightmare scenario we have not done nearly enough to prevent. Half of all prescriptions written for antibiotics in the US are still inappropriate and new medicines are barely trickling through clinical development. And now comes the MCR-1 gene, which renders bacteria resistant to colistin, the final antibiotic line of defense against recalcitrant infections like CRE. MCR-1’s ability to transfer resistance from one bacterial species to another may ultimately result in untreatable infections. How large is that risk? What will it take to prevent it?