Sexual dimorphism definitely exists in the pathogenesis of a variety of cardiovascular, neurodegenerative and bone metabolism disorders. Estrogen affects the healing of ischemic myocardium partially through paracrine growth hormone production by bone marrow mesenchymal stem cells (MSCs) and facilitation on mobilization of endothelial progenitors cells (EPCs) to the ischemic myocardium. Estrogen can also inhibit the proliferation of the cardiac fibroblasts. Therefore, estrogen effectively enhances the neovascularization at the ischemic border zone and limits pathological myocardial remodeling. Moreover, estrogen increases proliferation of embryonic neural stem cells and accelerates differentiation of neurons during neurogenesis, suggesting a possible role of estrogen in transplantation of neural stem cells as a therapeutic approach for neurodegenerative diseases. Finally, estrogen can modulate osteogenic progenitors and osteoclasts, preventing the osteoporosis. In general, estrogen offers significant benefits on diverse stem/progenitor cell populations. A great understanding of estrogens on these cells and relevant intracellular mechanisms will allow modulation of the potent stem cells directly for the ultimate clinical applications.