Despite a shift to noninvasive respiratory support, mechanical ventilation remains an essential tool in the care of critically ill neonates. The availability of a variety of technologically advanced devices with a host of available modes and confusing terminology presents a daunting challenge to the practicing neonatologist. Many of the available modes have not been adequately evaluated in newborn infants and there is paucity of information on the relative merits of those modes that have been studied. This review examines the special challenges of ventilating the extremely low birth weight infants that now constitute an increasing proportion of ventilated infants, attempts to provide a simple functional classification of ventilator modes and addresses the key aspects of synchronized ventilation modes. The rationale for volume-targeted ventilation is presented, the available modes are described and the importance of the open-lung strategy is emphasized. The available literature on volume-targeted modalities is reviewed in detail and general recommendations for their clinical application are provided. Volume guarantee has been studied most extensively and shown to reduce excessively large tidal volumes, decrease incidence of inadvertent hyperventilation, reduce duration of mechanical ventilation and reduce pro-inflammatory cytokines. It remains to be seen whether the demonstrated short-term benefits translate into significant reduction in chronic lung disease. Avoidance of mechanical ventilation by means of early continuous positive airway pressure with or without surfactant administration may still be the most effective way to reduce the risk of lung injury. For babies who do require mechanical ventilation, the combination of volume-targeted ventilation, combined with the open-lung strategy appears to offer the best chance of reducing the risk of bronchopulmonary dysplasia.