Background: Studies in human as well as animal models indicate a gender-specific responsiveness of the immune and organ systems with regard to shock, trauma, and sepsis. Methods: A literature review was performed. Results: Cell-mediated immune responses and cardiovascular functions are suppressed in males following trauma hemorrhage, whereas they are maintained or even enhanced in females in the proestrus state of the estrus cycle. Experimental studies have demonstrated that divergent immune responses in males and females following adverse circulatory conditions are mediated by the gender-specific hormones testosterone and estrogen. Several clinical trials, however, failed to demonstrate a significant association of gender and inflammatory response. This may be explained by the heterogeneity of the population in terms of their hormonal status at the time of injury. Conclusions: With regard to the underlying mechanisms, receptors for sex hormones have been identified on various immune cells, suggesting direct effects of these hormones on immune function. Alternatively, indirect effects of sex steroids such as changes in cardiovascular responses or androgen- and estrogen-synthesizing enzymes might contribute to gender-specific immune responses. Clinical studies suggest that sex hormones, such as dehydroepiandrosterone, modulate the function of peripheral blood mononuclear cells also following abdominal surgery. Thus, sex hormones, receptor antagonists, and sex steroid-synthesizing enzymes might be useful in the future for modulating the complex immune responses after trauma hemorrhage and sepsis. © 2014 S. Karger GmbH, Freiburg.