The effects of estrogen and progestins on the vascular wall have drawn major medical attention, and significant controversy over various studies has been developed. Several experimental and observational studies have shown cardioprotective effects; however, prospective randomized trials showed an increase in cardiovascular events in postmenopausal women on estrogen/medroxyprogesterone acetate treatment. The most significant parameter for cardiovascular benefit of estrogen seems to be the interval since the onset of menopause. In the early postmenopausal years, estrogen has beneficial effects on the vascular wall by inhibition of atherosclerosis progression, whereas in the late postmenopause, adverse effects like upregulation of the plaque inflammatory processes and plaque instability may develop. The effects of progestins on the cardiovascular system are not as clear and may differ according to the choice of progestins that is used. The aim of this review is to summarize the effects of estrogen and progestins on the vascular wall and their clinical implications.