In recent years, the problem of resistance of Klebsiella pneumoniae to antimicrobial drugs has received increasing clinical attention. Klebsiella pneumoniae exhibits complex resistance to a wide range of antimicrobial drugs, and the relevant pathways and targets, such as by the production of β-lactamases for β-lactam antimicrobials, by modification of targets or enzyme-mediated drug modification for aminoglycoside antimicrobials, by target mutations and enhanced excretory pumps for quinolone antimicrobials, by target modifications or drug pump excretion mechanisms for tigecycline, by bacterial cellular surface lipopolysaccharide modification to reduce the binding capacity of mucins, by altering cell wall permeability or increasing excretory pump activity for tetracyclines and macrolides. In this review paper, the research progress of the resistance mechanism of Klebsiella pneumoniae to antimicrobial drugs was summarized to provide theoretical support for clinical treatment of Klebsiella pneumoniae infection and use of antimicrobial drugs.