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The influence of social relationships on health has been well documented for many years, yet identifying the physiological mechanisms responsible for these effects has proved more challenging. This review assesses the potential role of the serotonin system in affecting sensitivity to the health-related effects of the social environment. Building on recent studies of genetic variation in the serotonin system, particularly focusing on a polymorphism (5-HTTLPR) in the serotonin transporter gene, we provide evidence that activity within the serotonin system is critically involved in setting sensitivity to social experiences. Furthermore, we highlight the effects of the 5-HTTLPR on sensitivity to both positive and negative social experiences. In a positive environment, individuals with the short allele, and particularly the short/short genotype, function better psychologically than those with the long/long genotype. Conversely, when exposed to adverse environments or in the absence of social support, individuals with the short allele are at high risk for a variety of negative health outcomes. This serotoninergic involvement in social sensitivity seems to occur in concert with other neurochemical systems, such as the opioid system, which will also be discussed. Although this differential sensitivity to social experiences is initially determined in the brain, it has physiological effects on downstream pathways that more directly affect disease mechanisms, such as the hypothalamic-pituitary-adrenal axis, which is a particular focus of this review. The serotonin system, as indexed by the 5-HTTLPR, is an important link between the social environment and health.