Caveolin-1 is a ubiquitously expressed integral membrane protein and essential for the formation of so-called Caveolae, small invaginations of the plasma membrane. Caveolae are involved in major physiological functions of the mammalian cell, including endocytosis and transcytosis processes, signal transduction and cholesterol homeostasis. During the last decade, it became evident that Caveolin-1 plays a key role in cancer progression and metastasis. As it has also been described as a tumor suppressor, the plethora of intracellular processes Caveolin-1 contributes to remains to be fully identified. Differences in pathophysiological protein function have been ascribed to cell-specific roles of Caveolin-1 and to cancer stage dependency. An important aspect of the protein in terms of cancer cure seems to be its relevance as a prognostic marker and for induction of metastasis. These diverse functions of Caveolin-1 were expanded by recent data showing its role in radio- and chemoresistance of tumor cells, a new aspect this review will concentrate on. Since resistance of tumor cells to conventional treatment regimes is still a major obstacle in cancer treatment, new targeting approaches in combination with conventional radio- and chemotherapy are highly desirable and of great interest to improve cancer patient cure.