Caveolae are specialized plasma membrane subdomains visualized more than 50 years ago as cave-like invaginations at the cell surface. They are rich in cholesterol, glycosphingolipids, and lipid-anchored proteins. Their signaling and trafficking capabilities influence multiple cellular processes, and are believed to require caveolin-1, a major protein component of caveolae in most cell types. Today the structure and functions of caveolae are still the objects of intense research. Caveolin-1 is not anymore the only protein known to be required for caveolae formation, and functions for caveolin-1 outside of caveolae are being unveiled. Studying the phenotype of mice lacking caveolae has largely confirmed the roles attributed to this organelle and its defining protein. The consequences of mutation of ablation of caveolins in human disease are emerging. Recent evidence further suggests that caveolae and caveolin can be targeted for therapeutic purposes.