Trauma remains the major cause of deaths in the United States and in other developing countries. Moreover, a significant number of trauma victims who survive initial injury succumb subsequently because of sepsis and multiple organ failure (Bone, 1992; Nathens and Marshall, 1996; Baue et al., 1998; Marshall, 1999; Angele et al., 2000; Baue, 2000; Choudhry et al., 2003).Thus, sepsis and organ dysfunction continue to be the major cause of morbidity and mortality in trauma patients. Although intensive investigations during the past three decades have helped identify some of the mechanisms responsible for sepsis and organ dysfunction, despite all these efforts the prognosis of trauma patients remains elusive. Furthermore, these studies suggest that the postinjury pathogenesis is complex and is influenced by multiple factors.Among these, gender is suspected to be a major factor that plays a significant role in shaping the host response to injury (Schroder et al., 1998; Angele et al., 2000; Schroder et al., 2000; Croce et al., 2002; Yokoyama et al., 2002; Chaudry et al., 2003; George et al., 2003b; Choudhry et al., 2004). The primary aim of this article is to present a comprehensive summary of the studies dealing with the role of gender in response to trauma as well as to discuss potential targets that can be used to modulate endogenous levels of sex hormones to improve organ functions after experimental trauma. © 2006 Springer Science+Business Media, LLC.