© 2018 The Author(s). Despite efforts in prevention and intensive care, trauma and subsequent sepsis are still associated with a high mortality rate. Traumatic injury remains the main cause of death in people younger than 45 years and is thus a source of immense social and economic burden. In recent years, the knowledge concerning gender medicine has continuously increased. A number of studies have reported gender dimorphism in terms of response to trauma, shock and sepsis. However, the advantageous outcome following trauma-hemorrhage in females is not due only to sex. Rather, it is due to the prevailing hormonal milieu of the victim. In this respect, various experimental and clinical studies have demonstrated beneficial effects of estrogen for the central nervous system, the cardiopulmonary system, the liver, the kidneys, the immune system, and for the overall survival of the host. Nonetheless, there remains a gap between the bench and the bedside. This is most likely because clinical studies have not accounted for the estrus cycle. This review attempts to provide an overview of the current level of knowledge and highlights the most important organ systems responding to trauma, shock and sepsis. There continues to be a need for clinical studies on the prevailing hormonal milieu following trauma, shock and sepsis.