--- - |2 This research examined whether heightened neural activation to social cues confers adjustment advantages in supportive social contexts but adjustment disadvantages in stressful social contexts. Forty‐five adolescent girls were exposed to social exclusion during an fMRI scan and reported on parent–child relationship quality and depressive symptoms. Stressful parent–child relationships predicted subsequent depressive symptoms in girls with high and moderate but not low dorsal anterior cingulate cortex, subgenual anterior cingulate cortex, and anterior insula activation during exclusion. In the context of supportive parent–child relationships, however, neural activation to exclusion predicted particularly low levels of depressive symptoms. This support for a biological sensitivity to context model suggests the possibility of redirecting adolescent girls’ neural sensitivity to social cues toward more positive adaptation. - Journal of Research on Adolescence, EarlyView.