Respiration at birth depends on maturation changes in lung tissue architecture, cell differentiation, and gene expression. At the transcriptional level, maturation is controlled by the actions of a group of transcription factors mediating gene expression in the lung. A network of transcription factors regulates gene expression in the respiratory epithelium, which then influences cell maturation throughout the lung. Glucocorticoids (via the glucocorticoid receptor), acting primarily in the pulmonary mesenchyme, influence maturation in the respiratory epithelium. Elucidation of the intersecting pathways controlling perinatal lung function may provide opportunities to induce pulmonary maturation in preterm infants at risk for respiratory distress syndrome before birth, and will help identify genes and processes important for various aspects of lung function.