The endothelium plays a crucial role in the regulation of cardiovascular homeostasis through the release of vasoactive autacoids such as nitric oxide, prostacyclin, and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). Although the functional influence of NO and EDHF is sometimes reciprocal (i.e., their effects decrease or increase with the reduction in vessel diameter, respectively), recent insights led to the identification of caveolae and caveolin as common regulators of their production. In this review, we will first focus on the current understanding of the caveolin/eNOS paradigm and will then detail the most recent findings on the role of caveolae in driving EDHF-signaling pathways.