Purpose of review Multidrug-resistant (MDR) Gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are associated with poor clinical outcomes. These pathogens represent a global threat with few therapeutic options. In this review, we discuss current guidelines for the empiric management of HAP/VAP caused by MDR Gram-negative pathogens. Recent findings The incidence of MDR Gram-negative bacteria is rising among cases of nosocomial pneumonia, such that it is now becoming a significant challenge for clinicians. Adherence to international guidelines may ensure early and adequate antimicrobial therapy, guided by local microbiological data and awareness of the risk factors for MDR bacteria. Summary Due to the increasing prevalence of HAP/VAP caused by MDR Gram-negative pathogens, management should be guided by the local ecology and the patient's risk factors for MDR pathogens. The main risk factors are prior hospitalization for at least 5 days, prior use of broad-spectrum antibiotics, prior colonization with resistant pathogens, admission to hospital settings with high rates of MDR pathogens, and septic shock at the time of diagnosis with nosocomial pneumonia.