Prepubescent boys are, if anything, more likely than girls to be depressed. During adolescence, however, a dramatic shift occurs: between the ages of 11 and 13 years, this trend in depression rates is reversed. By 15 years of age, females are approximately twice as likely as males to have experienced an episode of depression, and this gender gap persists for the next 35 to 40 years. We offer a theoretical framework that addresses the timing of this phenomenon. First, we discuss the social and hormonal mechanisms that stimulate affiliative needs for females at puberty. Next, we describe how heightened affiliative need can interact with adolescent transition difficulties to create a depressogenic diathesis as at-risk females reach puberty. This gender-linked vulnerability explains why adolescent females are more likely than males to become depressed when faced with negative life events and, particularly, life events with interpersonal consequences.