VAP is clearly associated with an increased mortality, principally because of virulent pathogens such as P. aeruginosa. Part of the increased mortality may be due to inadequacies of antibiotic therapy. Apparent failure of antibiotic therapy has many causes; some are related to deficiencies of the antibiotic therapy, but others are unrelated. Antibiotic failure can be the result of persistence of the original causative organism because of resistance, inadequate local antibiotic levels, anatomic limitations, or to the development of superinfection, either pneumonia or extrapulmonary. Factors probably unrelated to the adequacy of antibiotic regimens include misdiagnosis of the source of infection or causative organism, SIRS associated with the VAP, and the immunocompetency of the host. The pattern of apparent failure can assist in determination of the cause. Four typical patterns are rapid early progression; persistent pneumonia; initial improvement followed by deterioration; and slow, progressive improvement. The deficiencies of tracheal aspirate cultures and portable chest radiographs make determination of the cause of apparent failure difficult by these methods. Therefore, more accurate but invasive or expensive tests are usually required to avoid spiraling empirical antibiotic therapy. Quantitative bronchoscopic cultures and chest CT scans are most likely to lead to an accurate evaluation and appropriate antibiotic changes.