For the last 4 decades, the question of how to manipulate the serotonergic system with drugs has been an important area of research in biological psychiatry, and this research has led to advances in the treatment of depression. Research on the association between various polymorphisms and depression supports the idea that serotonin plays a role, not only in the treatment of depression but also in susceptibility to depression and suicide. The research focus here has been on polymorphisms of the serotonin transporter, but other serotonin-related genes may also be involved.1–5 In the future, genetic research will make it possible to predict with increasing accuracy who is susceptible to depression. Much less attention has been given to how this information will be used for the benefit of individuals with a serotonin-related susceptibility to depression, and little evidence exists concerning strategies to prevent depression in those with such a susceptibility. Various studies have looked at early intervention in those with prodromal symptoms as well as at population strategies for preventing depression.6–11 Obviously, prevention is preferable to early intervention; moreover, although population strategies are important, they are ideally supplemented with preventive interventions that can be used over long periods of time in targeted individuals who do not yet exhibit even nonclinical symptoms. Clearly, pharmacologic approaches are not appropriate, and given the evidence for serotonin’s role in the etiology and treatment of depression, nonpharmacologic methods of increasing serotonin are potential candidates to test for their ability to prevent depression.