Physiologically, estrogens carry out a myriad of functions, the most essential being the regulation of the reproductive axis. Currently, it is also dogmatic that estrogens play an important role modulating energy balance and metabolism. In this sense, it is well known that low estrogens levels, occurring due to ovarian insufficiency, in conditions such as menopause or ovariectomy (OVX), are associated with increased food intake and decreased energy expenditure, leading to weight gain and obesity at long term. Concerning energy expenditure, the main effect of estradiol (E2) is on brown adipose tissue (BAT) thermogenesis. Thus, acting through a peripheral or a central action, E2 activates brown fat activity and increases body temperature, which is negatively associated with body weight. Centrally, the hypothalamic AMP-activated protein kinase (AMPK) mediates the E2 action on BAT thermogenesis. In this chapter, we will summarize E2 regulation of BAT thermogenesis and how this can influence energy balance and metabolism in general.