Pulmonary surfactant is an essential lipid-protein complex that stabilizes the respiratory units (alveoli) involved in gas exchange. Quantitative or qualitative derangements in surfactant are associated with severe respiratory pathologies. The integrated regulation of surfactant synthesis, secretion, and metabolism is critical for air breathing and, ultimately, survival. The goal of this review is to summarize our current understanding and highlight important knowledge gaps in surfactant homeostatic mechanisms.