Caveolae are the most abundant features of the plasma membrane of many vertebrate cells. The surface of adipocytes, skeletal muscle, and many other cell types is densely covered by these small invaginations. Membrane proteins of caveolae, called caveolins, work together with lipid-binding peripheral membrane proteins called cavins to generate caveolae. New insights into the structure of these key caveolar components is beginning to give insights into the molecular interactions involved in formation of caveolae and into their function. Using a number of experimental systems, including cultured cells, zebrafish, and mice, we have shown that caveolae represent a metastable surface domain, able to respond to a number of stimuli, including increased membrane tension, oxidative stress, and UV, by release of cavins into the cytoplasm. The released cavins can interact with intracellular targets to trigger specific cellular responses. Our recent work has revealed interactions of cavins with DNA repair proteins and with key regulators of oxidative stress. These results highlight a critical role for caveolae and the caveolin-cavin system as protective and stress signaling elements of the plasma membrane.