The diagnosis of ventilator-associated pneumonia, VAP, is problematic because of a lack of objective tools that are utilized to make an assessment of bacterial-induced lung injury in a heterogeneous group of hosts. Clinical symptoms and signs are used to identify patients that may have a "lung infection". However, the symptoms and signs can be produced by a myriad of other conditions. Recent clinical data also suggests bacterial-induced pathologic processes occur prior to the onset of the symptoms and signs. Utilizing bacterial culture alone, health care practitioners are forced to wait for days for results and will have to order days of empiric antibiotic therapy. Exploratory molecular studies utilizing clone libraries and molecular arrays for microbial identification document the inability of culture-based techniques to even identify all the microbes involved in VAP. These molecular studies also offer evidence that oral flora present in the lungs of patients with VAP, suggesting aspiration of oral secretions and/or biofilms on endotracheal tubes, supply the bacteria for VAP. Much more investigation is needed to determine the optimal timing of antibiotic treatment and which diagnostic molecular methods can be utilized in the ICU.