Postmortem human and animal studies provided important insights into the relationship between histology and bacteriology in VAP. According to the results of these studies, VAP is a multifocal and polymicrobial infectious process. The lesions are predominately located in dependent segments of lower lobes. There is no straightforward relationship between the intensity of lung damage and the local microbial burden. Histobacteriologic discrepancy may explain why even such techniques as PSB and BAL can be unreliable for the diagnosis of VAP. The histopathologic examination of the lung tissue has been traditionally regarded as the gold standard for diagnosis of VAP. Even with histology, however, pneumonia is frequently difficult to define. For daily practice, antimicrobial decisions and the guidance of antimicrobial regimens should not rely exclusively on the results of quantitative cultures in the individual patient. Instead, finding a balance between clinical judgment and microbiologic results is crucial to manage patients with VAP appropriately.