Ventilator-induced lung injury has been established as a significant risk to patients receiving PPV. Animal studies have provided definitive experimental data that support the existence of VILI. Clinical studies have implied the role of VILI in ARDS and ALI patients. In patients who have ARDS or ALI, however, VILI cannot be distinguished from exacerbation of the primary condition. Animal and clinical studies that clearly show elevated levels of cytokines when PPV is applied beyond certain limits support the concept that an inflammatory process is activated by PPV. Whether the induction of inflammatory mediators contributes to the mortality or morbidity of the ventilated patient has not been established. A potential role for anti-inflammatory therapeutic agents is promising. Therefore, the following considerations can guide the clinical care of ventilator patients: Alveolar pressure exposure (plateau pressure) should be limited to less than 32 cm H2O. Positive end-expiratory pressure should be applied to avoid end-expiratory collapse and reopening. Tidal volume should be set at approximately 6 mL/kg or further guided by plateau pressure limitation. Although studies suggest that reducing Ti, flow, and f may be important in avoiding VILI, there are no current guidelines. The results of preliminary studies investigating the preventative potential of respiratory acidosis, prone positioning, or careful vascular pressure management seem promising. Inflammatory response in VILI has been established, but a role for intervention, such as general or specific suppression of the response, has not been established.