Working memory (WM) is a key process that is integral to many complex cognitive tasks, and it declines significantly with advancing age. This review will survey recent evidence supporting the idea that the functioning of the WM system in women is modulated by circulating estrogens. In postmenopausal women, increased estrogen concentrations may be associated with improved WM function, which is evident on WM tasks that have a high cognitive load or significant manipulation demands. Experimental studies in rhesus monkeys and human neuroimaging studies support a prefrontal locus for these effects. Defining the basic neurochemical or cellular mechanisms that underlie the ability of estrogens to regulate WM is a topic of current research in both human and animal investigations. An emerging body of work suggests that frontal executive elements of the WM system are influenced by the circulating estrogen concentrations currently available to the CNS and that the effects are region-specific within the frontal cortex. These findings have implications for women's brain health and cognitive aging.