For100 years, researchers and medical professionals have been aware of a gender difference in immune responsiveness following insults like trauma, shock, burn or sepsis. Strong experimental evidence indicates that female animals are protected under such conditions compared to their male counterparts. 17-estradiol (estrogen) is reported to be responsible for those protective effects as studies have shown that estrogen administration plays a major role in the restoration and maintenance of cellular and organ function following injury. Numerous experimental studies have also shown a variety of salutary effects of estrogen under low-flow conditions; however, clinical studies are rare and observational studies are inconclusive, even though a trend towards an advantage for females has been shown. Nonetheless, further clinical studies are needed as estrogen administration is simple and a single-dose administration of this hormone is not expected to produce any adverse effects. Thus, treatment of traumatized patients with estrogen could prove to be a simple, yet powerful, therapeutic option which may find its way into programs for the management and care of the traumatized host.