Mechanical ventilation of patients undergoing thoracic surgery is often challenging. These patients frequently have significant underlying comorbidities, including cardiopulmonary disease, and often must undergo 1-lung ventilation. Perioperative respiratory complications are common and are multifactorial in etiology. Increasing evidence suggests that mechanical ventilation is associated with, and may even cause, lung damage in both sick and healthy patients. Gas exchange to provide acceptable end-organ oxygenation remains a primary goal but so too is minimization of risks for acute lung injury. Every ventilator strategy is associated with potential beneficial and adverse side effects. Understanding the impact of various ventilation strategies allows clinicians to provide optimal care for patients.