Individual health is determined by a myriad of factors. Interestingly, simply being male or female is one such factor that carries profound implications for one's well-being. Intriguing differences between men and women have been observed with respect to vulnerability to and prevalence of particular illnesses. The activity of the major stress hormone axis in humans, the hypothalamus-pituitary-adrenal axis, is directly and indirectly associated with the onset and propagation of these conditions. Previous studies have shown differences between men and women at the level of stress hormone regulation, suggesting that the metabolic effects of stress may be related to susceptibility for stress-related disease. While the majority of studies have suggested that biological differences are responsible, few have also considered the role of gender socialization. In this selective review, the authors summarize evidence on sex differences and highlight some recent results from endocrinological, developmental, and neuroimaging studies that suggest an important role of gender socialization on the metabolic effects of stress. Finally, a model is proposed that integrates these specific findings, highlighting gender socialization and stress responsivity.