Functional evidence for the existence of plasma membrane estrogen receptors in a variety of cell types continues to accumulate. Many of these functions originate from rapid signaling events, transduced in response to 17β-estradiol (E₂). It has been convincingly shown that E₂ activates phosphoinositol 3-kinase and protein kinase B/AKT, and stimulates ERK and p38 MAP kinases. In part, this stems from G-protein activation and the resulting calcium flux. As a result, the link between E₂ action at the cell membrane and discrete biological actions in the cell has been strengthened. There is now convincing in vitro evidence that E₂ can modulate the functions of neural and vascular cells via non-genomic actions. Thus, the actions of discrete pools of E₂ receptors are likely to contribute to the overall effects of the sex steroids.