Conventional mechanical ventilation continues to be the standard mode of support for neonates with respiratory failure. Controversies regarding the selection of optimal ventilatory strategies still abound. A deep understanding of physiologic concepts as well as a critical appraisal of the literature is needed to optimize the ventilatory management of the newborn. Principles of gas exchange, pulmonary mechanics and control of breathing are reviewed in the context of their relevance during mechanical ventilation. The application of these concepts to the ventilatory strategies for the management of infants with respiratory distress is presented, and current controversies are emphasized.