This review addresses the physiological background and the current status of evidence regarding ventilator-induced lung injury and lung protective strategies. Lung protective ventilatory strategies have been shown to reduce mortality from adult respiratory distress syndrome (ARDS). We review the latest knowledge on the progression of lung injury by mechanical ventilation and correlate the findings of experimental work with results from clinical studies. We describe the experimental and clinical evidence of the effect of lung protective ventilatory strategies and open lung strategies on the progression of lung injury and current controversies surrounding these subjects. We describe a rational strategy, the open lung strategy, to accomplish an open lung, which may further prevent injury caused by mechanical ventilation. Finally, the clinician is offered directions on lung protective ventilation in the early phase of ARDS which can be applied on the intensive care unit.