© 2015 © 2015 Taylor & Francis. Introduction: Gender is increasingly recognized as a key factor in trauma and sepsis. Multiple clinical and experimental studies on sepsis have shown a distinct advantage of females in the proestrus cycle to survive sepsis compared with age-matched males. In addition, estrogen treatment is beneficial in non-proestrus cycles and also in ovarectomized females. In this manuscript, the effects of gender and sex hormones in sepsis are summarized and potential gender-specific therapeutic strategies in women are evaluated.Areas covered: This review comprises current clinical studies on the effect of gender in sepsis and gives an overview on gender and sex hormone-related effects on immune cells and organ function. Based on clinical and experimental data, potential therapeutic targets are presented.Expert opinion: Estrogens and estrogen-receptor agonists have been extensively shown to be beneficial in the setting of sepsis. Clinical data, however, do not clearly support their therapeutic use. This discrepancy appears to be mainly due to insufficient study design in clinical trials conducted up to now. Therefore, improved study protocols with exact analysis of the patients hormonal status are needed to clarify the role of gender and sex hormones in trauma and sepsis.