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Abstract ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are among the most common opportunistic pathogens in nosocomial infections. ESKAPE pathogens distinguish themselves from normal ones by developing a high level of antibiotic resistance that involves multiple mechanisms. Contemporary therapeutic strategies which are potential options in combating ESKAPE bacteria need further investigation. Herein, a broad overview of the antimicrobial research on ESKAPE pathogens over the past five years is provided with prospective clinical applications.