Prior to adolescence, the rates of depression are similar in girls and boys, or are slightly higher in boys. However, with the onset of puberty, the gender proportion of depression dramatically shifts to a 2:1 female to male ratio. What is the relationship between menarche and the onset of major depression in early adolescence? A recent theoretical model proposes that vulnerability to depression may be rooted in normal female hormonal maturational processes and gender socialization. Information regarding the management of depression in adolescent and young adult women is provided, including gender differences in the presentation of depressive symptoms, instruments to facilitate assessment, and treatment options. Pubertal and other hormonal changes should be monitored prospectively along with individual, genetic, constitutional, and psychological characteristics. The burden of illness associated with onset of depression following menarche reinforces the importance of expeditious recognition and intervention.