The recent widespread emergence of multidrug‐resistant and extensively-drug-resistant Gram-negative bacteria is an important public health challenge worldwide. Confronted with diminishing therapeutic options, colistin (polymyxin E) is increasingly being used by clinicians as a last-line agent for treating infections with these important pathogens. Colistin is a potent cationic peptide which interacts with the anionic lipid A moiety of the Gram-negative lipopolysaccharide structure to promote membrane permeability, cellular leakage and subsequent bacterial death. However, the renewed clinical use of this agent, coupled with its widespread agricultural use in some countries has driven the rapid dissemination of K. pneumoniae strains showing resistance to colistin. Here we will discuss the recent research findings from our group and elsewhere to: i) highlight the global epidemiology and evolution of colistin resistance in K. pneumoniae, ii) outline the molecular mechanisms involved in both chromosomal- and plasmid-mediated K. pneumoniae colistin resistance, and iii) consider the implications for treatment outcomes and future surveillance strategies.