The spread of resistant bacteria has caused serious concern worldwide. The spread of Multidrug-Resistant (MDR) bacteria limits the choice of antibiotics, making those available less effective. Such bacterial infections increase morbidity and mortality, lengthen hospital stays, and increase healthcare expenses. Nosocomial pathogenic microorganisms, known as ESKAPE pathogens exhibit multidrug resistance and increased levels of pathogenicity. These pathogens are associated with high morbidity, mortality, and prolonged hospital stays, posing a serious threat to public health. The rapid emergence and spread of Multidrug Resistant (MDR) strains have outpaced the development of new antibiotics, challenging treatment strategies and infection control measures. Addressing the threat of ESKAPE pathogens requires a multifaceted approach involving antimicrobial stewardship, stringent infection prevention practices, rapid diagnostics, and innovative therapeutic alternatives. The aim of this paper is to review antibiotic resistance in ESKAPE pathogens.