Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) represent a growing problem. Indeed, ESBL-PE is endemic in many countries, and 5 to 25% of intensive care unit (ICU) patients are ESBL-PE carrier on ICU admission. ESBL-PE HAP/VAP is associated with a higher mortality than HAP/VAP due to susceptible Enterobacteriaceae because the resistance profile decreases the adequacy rate of empiric therapy. ESBL-PE should be considered in the empirical treatment in case of the high burden of ESBL-PE in the unit, in the case of previous ESBL-PE colonization, when the HAP/VAP occurs late, and in patients with shock. A negative active systematic surveillance culture on rectal swab reduced the risk of ESBL-PE VAP to less than 1%. Rapid diagnostic tests are now able to confirm the presence of ESBL-PE in VAP within 24 hours; new molecular methods will provide results within few hours.Adequate treatment usually required carbapenems. The alternative β-lactams such as β-lactams/β-lactamases inhibitor combinations could be proposed as a step-down therapy according to the antibiotic susceptibility result. Optimization of pharmacokinetics requires high dosage and continuous or prolonged infusions for β-lactams. When the patient is stabilized, a therapy of duration 7 to 8 days is recommended.