Increasing use of colistin for multidrug-resistant Gram-negative bacterial infections has led to the emergence of colistin resistance in Klebsiella pneumoniae in several countries worldwide, including Europe (especially Greece), and colistin resistance rates are continually increasing. Heteroresistance rates, which were significantly higher than resistance rates, were found to be important. Although the mechanism underlying resistance is unclear, it has been suggested that it is related to lipopolysaccharide modification via diverse routes. Several factors have been reported as being associated with colistin resistance, with improper use and patient-to-patient transmission being most often cited. Total infections and infection-related mortality from colistin-resistant K. pneumoniae are high, but currently there are no established treatment regimens. However, several combination regimens that are mainly colistin-based have been found to be successful for treating such infections.