Stress-related psychiatric disorders, such as anxiety and trauma-related disorders, occur twice as frequently in women as in men. These disorders share hyperarousal as a core feature and stress as an etiological factor, suggesting that sex differences in stress modulation of arousal circuitry may underlie this sex bias. The stress neuropeptide corticotropin-releasing factor (CRF) innervates brain arousal centers, including the locus coeruleus (LC)-norepinephrine system. Previously, we found that LC neurons are more sensitive to CRF in female than in male rats. This effect is linked to sex differences in CRF1 receptor signaling and trafficking. For example, stressor exposure in rats and CRF overexpression in mice cause CRF1 receptor internalization in males only, suggesting that females lack this important cellular adaptation. This sex difference is associated with increased LC neuronal firing in female, but not male CRF overexpressing mice. Sex differences in CRF function are now being linked to sex differences in behaviors mediated by arousal level, including attention. To this end, the ability of central CRF administration to modulate performance on a sustained attention task was examined in male and female rats. CRF impaired sustained attention in both males and females. In addition, females were unable to sustain vigilance over the testing session, while the performance in males remained stable. Females also omitted more trials, presumably reflecting a lower motivation to perform under stressful conditions than males. Collectively, these studies suggest that molecular sex differences in the CRF1 receptor are linked to specific sex differences behavior. If true in humans, sex differences in CRF modulation of arousal systems may be an important determinant of female vulnerability to stress-related psychiatric disorders.