Background: Loneliness is assumed to peak in early adolescence and to decrease throughout middle and late adolescence, but longitudinal confirmation of this tendency is lacking. Behavioral genetic studies with twin designs have found a significant genetic component for loneliness in children and adults, but no molecular genetic studies have been conducted to reveal the functional polymorphisms involved. Methods: Associations among the serotonin transporter gene (5-HTTLPR), sex, parental support, and loneliness were examined in a longitudinal study spanning five annual waves (N = 306). Results: Using latent growth curve modeling (LGCM), loneliness was found to be highest in early adolescence and slowly declined throughout adolescence. The 5-HTTLPR genotype was related to the development of loneliness, in that short allele carriers remained stable in loneliness over time, whereas adolescents with the long-long genotype decreased in loneliness. Interactions were found between maternal support and 5-HTTLPR genotype, showing that adolescents who perceived little support from their mothers and carried a short allele were at increased risk for developing loneliness. Conclusions: Our study is the first to chart adolescent loneliness longitudinally and to examine the genetic underpinnings of loneliness. Our results contribute to a further understanding of the environmental and genetic basis of loneliness. Replication of our results is needed in both population-based and clinical samples.