Protracted mechanical ventilation is associated with increased morbidity and mortality in preterm infants and thus the earliest possible weaning from mechanical ventilation is desirable. Weaning protocols may be helpful in achieving more rapid reduction in support. There is no clear consensus regarding the level of support at which an infant is ready for extubation. An improved ability to predict when a preterm infant has a high likelihood of successful extubation is highly desirable. In this article, available evidence is reviewed and reasonable evidence-based recommendations for expeditious weaning and extubation are provided.