Estrogen explicates several functions on the cardiovascular system through binding to estrogen receptors (ERs). Traditionally, ERs play their role as transcription factors, which regulate the expression of target genes. In the past decades, however, a lot of studies revealed rapid estrogen's actions in non-reproductive tissues such as the cardiovascular system where estrogen induce "extra-nuclear actions" that not require gene expression or protein synthesis, independently of the nuclear localization of ERs such as rapid vasodilatation, anti-inflammatory effects, vascular cell growth and migration, and protection to cardiomyoctyes. Indeed, some of these actions are defined by ERs residing at or near the plasma membrane. ERs interact with membrane-associated signaling molecules such as ion channels, G proteins, the tyrosine kinase c-Src, liganded extra-nuclear, leading to the activation of downstream cascades such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-OH kinase (PI3K). These cascades are responsible for important cardiovascular actions of estrogen, for instance, the activation of nitric oxide synthesis or the remodeling of endothelial actin cytoskeleton. Moreover, these cascades play crucial roles in regulating the expression of target proteins implicated in cell proliferation, apoptosis, differentiation, movement and homeostasis. The recent improvements in the characterization of the molecular basis of the extra-nuclear signaling of estrogen helps to understand the biological functions of estrogen, and would be beneficial to elucidate current controversies on estrogen's clinical efficacy in cardiovascular system.