Steroid receptors existing outside the nucleus are increasingly being recognized in many organs and cell types, impacting the biology of bone, the heart and blood vessels, and the central nervous system. Some controversy exists as to the nature of the receptors at the plasma membrane. However, compelling evidence has been advanced that at least some classical steroid receptors mediate steroid ligand actions originating as signaling from the cell surface. Here I review the recent findings in this evolving field emphasizing the in vivo impact of these receptor pools with a focus on estrogen receptors.