A number of cellular and biochemical processes are involved in the pathophysiology of glomerular and vascular remodeling, leading to renal and vascular disorders, respectively. Although estradiol protects the renal and cardiovascular systems, the mechanisms involved remain unclear. In this review we provide a discussion of the cellular, biochemical, and molecular mechanisms by which estradiol may exert protective effects on the kidneys and vascular wall. In this regard, we consider the possible role of genomic vs. nongenomic mechanisms and estrogen receptor-dependent vs. estrogen receptor-independent mechanisms in mediating the protective effects of estradiol on the renal and cardiovascular systems.