Endothelial caveolae are essential for a wide range of physiological processes and have emerged as key players in vascular biology. Our understanding of caveolar biology in endothelial cells has expanded dramatically since their discovery revealing critical roles in mechanosensation, signal transduction, eNOS regulation, lymphatic transport, and metabolic disease progression. Furthermore, caveolae are involved in the organization of membrane domains, regulation of membrane fluidity, and endocytosis which contribute to endothelial function and integrity. Additionally, recent advances highlight the impact of caveolae-mediated signaling pathways on vascular homeostasis and pathology. Together, the diverse roles of caveolae discussed here represent a breadth of cellular functions presenting caveolae as a defining feature of endothelial form and function. In light of these new insights, targeting caveolae may hold potential for the development of novel therapeutic strategies to treat a range of vascular diseases.