Management of antimicrobial resistance in multi-drug-resistant-Klebsiella pneumoniae (MDR-KP) is a major challenge for clinicians. The optimal treatment option for MDR-KP infections is still not well established. Combination therapies including high-dose meropenem, colistin, fosfomycin, tigecycline, and aminoglycosides are widely used, with suboptimal results. New antimicrobials targeting MDR-KP have been developed during the last decades and are now at various stages of clinical research. Areas covered: The PubMed database was searched to review the most significant literature on the topic, with a special consideration for articles coming from endemic countries. Expert commentary: We reviewed the currently available treatment options, discussing the characteristics of new antibiotics with activity against MDR Gram-negative bacteria and the strategies for preventing the spread of MDR-KP. While we wait for real-world data from novel compounds, coordinated strategies and common efforts in infection control and stewardship programs remain the cornerstone for limiting, or potentially reversing, conditions that favor the spread of MDR-KP.