Long-term and excessive use of antibiotics has caused the spread of antibiotic resistance. The time- and cost-consuming process of new antibiotic development results in the much slower emergence of new antibacterial drugs than that of bacterial resistance. The emergence of superbugs has been growing to become a dominant challenge in human health. Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Tigecycline resistance of Klebsiella pneumoniae remains a global problem that urgently needs to be solved.