The article discusses the growing problem of antibiotic resistance in *Klebsiella pneumoniae* (Kp), a common gram-negative bacteria causing severe infections. Due to antibiotic overuse, Kp has developed multidrug resistance (MDR), making it a global health threat. The article reviews the mechanisms of Kp's antibiotic resistance, including intrinsic and acquired resistance, and explores potential new drug targets for effective treatment. Kp's resistance mechanisms include the production of β-lactamases, which inactivate antibiotics like cephalosporins and carbapenems. Other mechanisms involve porin loss, which limits antibiotic entry, and the overexpression of efflux pumps, which expel drugs from the cell. Biofilm formation also contributes to resistance by protecting bacteria from antibiotics and promoting genetic exchange. Acquired resistance in Kp is often due to the horizontal transfer of resistance genes, particularly through plasmids. The emergence of carbapenem-resistant Kp (CRKP) is a major concern, as these strains are resistant to many antibiotics. The article also highlights the role of various resistance genes, such as KPC, NDM, and VIM, which are associated with high mortality rates. The article emphasizes the urgent need for new antibiotics and alternative therapies to combat MDR Kp. It explores potential drug targets, including enzymes involved in fatty acid biosynthesis, lipid A production, and cell wall formation. These targets are promising because they are essential for bacterial survival and are not present in human cells, reducing the risk of toxicity. The review also discusses the challenges in developing new antibiotics, including the high cost and low profit margins, and the need for innovative approaches to drug discovery. Overall, the article underscores the importance of understanding Kp's resistance mechanisms to develop effective treatments and strategies to combat this growing public health crisis.The article discusses the growing problem of antibiotic resistance in *Klebsiella pneumoniae* (Kp), a common gram-negative bacteria causing severe infections. Due to antibiotic overuse, Kp has developed multidrug resistance (MDR), making it a global health threat. The article reviews the mechanisms of Kp's antibiotic resistance, including intrinsic and acquired resistance, and explores potential new drug targets for effective treatment. Kp's resistance mechanisms include the production of β-lactamases, which inactivate antibiotics like cephalosporins and carbapenems. Other mechanisms involve porin loss, which limits antibiotic entry, and the overexpression of efflux pumps, which expel drugs from the cell. Biofilm formation also contributes to resistance by protecting bacteria from antibiotics and promoting genetic exchange. Acquired resistance in Kp is often due to the horizontal transfer of resistance genes, particularly through plasmids. The emergence of carbapenem-resistant Kp (CRKP) is a major concern, as these strains are resistant to many antibiotics. The article also highlights the role of various resistance genes, such as KPC, NDM, and VIM, which are associated with high mortality rates. The article emphasizes the urgent need for new antibiotics and alternative therapies to combat MDR Kp. It explores potential drug targets, including enzymes involved in fatty acid biosynthesis, lipid A production, and cell wall formation. These targets are promising because they are essential for bacterial survival and are not present in human cells, reducing the risk of toxicity. The review also discusses the challenges in developing new antibiotics, including the high cost and low profit margins, and the need for innovative approaches to drug discovery. Overall, the article underscores the importance of understanding Kp's resistance mechanisms to develop effective treatments and strategies to combat this growing public health crisis.