Lung surfactant covers and stabilizes a large, delicate surface at the interface between the host and the environment. The surfactant system is placed at risk by a number of environmental challenges such as inflammation, infection, or oxidant stress, and perhaps not surprisingly, it demonstrates adaptive changes in metabolism in response to alterations in the alveolar microenvironment. Recent experiments have shown that certain components of the surfactant system are active participants in the regulation of the alveolar response to a wide variety of environmental challenges. These components are capable not only of maintaining a low interfacial surface tension but also of amplifying or dampening inflammatory responses. These observations suggest that regulatory molecules are capable of both sensing the environment of the alveolus and providing feedback to the cells regulating surfactant synthesis, secretion, alveolar conversion, and clearance. In this review we examine the evidence from in vitro systems and gene-targeted mice that two surfactant-associated collectins (SP-A and SP-D) may serve in these roles and help modify surfactant homeostasis as part of a coordinated host response to environmental challenges.