It is now firmly established that estrogen and all sex steroid receptors exist in discrete cellular pools outside the nucleus. Estrogen receptors (ER) have been localized to the plasma membrane where both ERalpha and ERbeta function in a wide variety of cells and organs. ERs have also been found in discrete cytoplasmic organelles including mitochondria and the endoplasmic reticulum. In ligand-dependent fashion, each ER pool contributes to the overall, integrated effects of estrogens producing biological outcomes. This review highlights the recent work establishing new roles and targets of membrane ER signaling. Such actions include prevention of vascular injury or cardiac hypertrophy, sexual behavior and pain perception mediated through the central nervous system, osteoblast survival, and fluid resorption in the colon.