Spiritual awakening is inherent to development in the second decade, as reflected not only in millennia of religious faith traditions and indigenous culture but also in recent genetic-twin and epidemiological studies. Developmentally concomitant with spiritual awakening is the window of onset for the most prevalent forms of adolescent suffering in post-industrial societies: depression and related substance abuse and risk taking. Over the past fifteen years, spirituality-a lived relationship with a Higher Power-has been found to be the most robust protective factor against depression known to medical and social sciences. The magnitude of the protective effect and its timing in adolescence raises the question of a singular process or shared biological substrate underlying spiritual awakening and onset of depression. Evidence for such a shared physiology comes from a recent magnetic resonance imaging (MRI) study suggesting that depression and spirituality in youth reveal "two sides of the same coin."