Ventilator-associated pneumonia is a serious hospital-acquired infection, with 20-70% crude mortality and 10-40% estimated attributable mortality. Insufficient antibiotic concentrations at the infection site when these drugs are given intravenously may lead to poor outcomes, particularly when difficult-to-treat pathogens are responsible; for example, Pseudomonas aeruginosa, extended spectrum beta lactamase-producing Gram-negative bacilli, Acinetobacter spp. and/or methicillin-resistant Staphylococcus aureus. Direct drug delivery to the infection site via aerosolization combined with intravenous administration achieves concentrations exceeding MICs of the pathogens, even those with impaired susceptibility. Experimental and recent clinical results demonstrated our markedly improved ability to deliver aerosolized antibiotics to the lung with new-generation devices, for example, vibrating-mesh nebulizers. Convincing clinical data from a large randomized trial are still lacking to support the routine administration of aerosolized antibiotics to treat ventilator-associated pneumonia, even though some small-randomized trials' observations are encouraging.