Carbapenem-resistant Klebsiella pneumoniae (CRKP) leads to high mortality of infected patients. How to deal with CRKP is an urgent problem in clinical practice, and it is imperative to carry out researchon carbapenem resistance mechanism of CRKP. The two-component systems (TCSs) areassociated with the development of drug resistance in a variety of bacteria, and TCSs were expected to be important therapeutic targets for CRKP. Therefore, this article reviewed the mechanisms of TCSs in the regulation of CRKP from the following several aspects: common mechanisms of carbapenem resistance of CRKP, research progress in drug resistance of TCSs, relationships between Klebsiella pneumoniae and TCSs, and so on. It may provide some research ideas for future research and the references for clinical diagnosis and treatment.