Phospholipids have the major role in pulmonary surfacant concerning its biophysical function of reducing surface tension at the alveolar air-liquid interface to facilitate respiratory mechanics. However, the presence of some specific, highly hydrophobic polypeptides is essential to modulate the physical behavior of phospholipids and to promote rapid formation of stable surface films that are able to produce surface tensions in the range of 0 dynes/cm during cyclic compression. The present review summarizes the available data on the parameters governing lipid-protein interactions of the hydrophobic surfactant proteins SP-B and SP-C with the main surfactant phospholipids. Lipid-protein interactions in surfactant have been studied in vitro using preparations reconstituted with very different methodological procedures. Conclusions concerning the role of hydrophobic surfactant proteins on the assembly of lipid-protein surfactant structures in vivo have been revised in this respect. This review presents the knowledge available on the disposition of SP-B and SP-C in surfactant structures, the mode, extent, selectivity, and stoichiometry of their lipid-protein interactions, and the effect of the proteins on structure and dynamics of surfactant bilayers and monolayers. Some considerations are given to possible concerted actions, under physiological conditions, of both proteins SP-B and SP-C.