Estradiol (E2) is traditionally recognised as the female sex hormone. Since discovery of estrogens in the early forties of XX century it has been believed, that these hormones caused impairment of the gonadal function in men or didn't exert any influence. New studies are contradictory, but indicate also a possible involvement of estrogens in the pathogenesis of some systemic diseases of men. The main source of E2 in men is adipose tissue and the brain. E2 is also produced in adrenals, liver, mammary glands, hair and in male gonads. Daily production and blood level of E2 in men are higher than those in postmenopausal women. In 1988 we were the first to demonstrate that E2 is an important hormonal signal for initiation of spermatogenesis. The traditional view about unimportant or inhibitory role of E2 in male physiology was finally refuted thanks to discovery of the estrogen receptors in males. In the middle 90ties transgenic mice with the lack of estrogen receptor (ER knockout) or enzyme aromatase, that enable the conversion of testosterone into E2, were produced. Observations of men with inherited mutations of these genes, considerably extended our knowledge about stimulatory role of E2 in men in the formation of bone stroma, inhibition of their linear growth, lipids metabolism and sexual maturation, the effects that were attributed to testosterone action until today. New data indicate role of estrogens and ER in the function of the cardio-vascular system. Their link with development of arteriosclerosis seems, however, to be bipolar. In single reported cases of men with the inactivating mutations of ERalpha or aromatase genes, a precocious arteriosclerosis is noted. From the other site, men homozygous for the most common variant of ERalpha gene (ESR1c.454-397cc) have a significantly increased risk of myocardial infraction. Estrogens are the risk factors in prostatic cancer and their local tissue increase in autoimmune diseases is connected with aggravation of the proliferative complications of these disorders.