VAP remains the most common nosocomial infection among critically ill patients and is associated with substantial clinical and economic burden. The diagnosis of VAP requires an integrated assessment of clinical, radiological, and microbiological data, as no single tool—whether a clinical score, biomarker, or imaging modality—provides sufficient diagnostic accuracy. Pre-antibiotic quantitative cultures remain a cornerstone of diagnosis. Lung ultrasound offers a valuable bedside adjunct. Multiplex PCR panels can accelerate the identification of pathogens and resistance genes, but require cautious interpretation. VAP is a biologically heterogeneous syndrome, and emerging data on host-response endotypes and transcriptomic signatures may ultimately enable more precise diagnostic and therapeutic strategies. Preventive strategies are primarily non-pharmacological and relatively straightforward to implement; however, they are often underutilized or inconsistently applied in routine practice. Endotracheal tube (ETT) biofilm formation represents a key pathophysiological mechanism, underpinning both the rationale for ETT-based preventive devices and the challenges in eradicating established infection. Pharmacological approaches—mainly selective digestive decontamination (SDD) and targeted antibiotic prophylaxis in high-risk subgroups—have demonstrated efficacy in reducing VAP incidence. However, the largest randomized controlled trial to date (SuDDICU) did not show a mortality benefit associated with SDD.

Future research priorities include establishing a widely accepted diagnostic gold standard; better characterizing host response and the pulmonary microbiome in early infection; clarifying the role of molecular diagnostics; identifying patient endotypes associated with treatment failure; and refining which subpopulations benefit from pharmacological prophylaxis. Predictive models integrating multimodal data may enable more targeted antibiotic use and help mitigate overtreatment.