Mechanical ventilation is a key therapeutic intervention in critically ill patients, particularly those with acute lung injury or Acute Respiratory Distress Syndrome. Among several ventilation strategies, variable pressure support ventilation is physiologically compelling and has shown promising results in preclinical investigations. In this review we outline the major studies that led to the development of variable ventilation in the early 1990s and offer a definition for the term "variability". Furthermore, we depict assisted ventilation modes that enhance the variability of the respiratory pattern and describe the current understanding of mechanisms of variable ventilation. Finally, we discuss potential harms of variable ventilation. Variable ventilation seems to enhance pulmonary function and reduce lung damage and inflammation compared to monotonic ventilation modes, but these findings are based on experimental data. Clinical trials are needed to confirm or refute the putative beneficial effects of variable ventilation. © 2012, Nederlandse Vereniging voor Intensive Care. All Rights Reserved.