Four decades of research have examined the antecedents and consequences of behavioral inhibition (BI), a temperament profile associated with heightened reactivity to sensory stimuli in infancy, reticence toward social cues in childhood, and the later emergence of social anxiety in adolescence. This review proposes that a two-hit model can supplement prior work to better understand these developmental pathways. Specifically, time limited experiences (“hits”) centered in infancy and adolescence stress idiosyncratic BI-linked processes that uniquely trigger the developmental pathway from temperament to disorder. To illustrate, we focus on caregiver distress in infancy (including fetal development), social reorientation in adolescence, and their impact on malleable attentional and cognitive systems. These are developmental challenges and processes that go to the heart of the BI phenotype. Finally, we note open questions in this conceptual model, potential caveats, and needed future research. Expected final online publication date for the Annual Review of Developmental Psychology, Volume 5 is December 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.