Pediatric depression is an important clinical problem that is known to be familial. Twin studies have been used not only to examine the genetic etiology of depression but also to investigate developmental changes and gender effects, the relationship of depression with anxiety, and increasingly, the interplay of genetic liability with environmental risk factors. There is evidence that pediatric depression symptom scores and clinical depression are genetically influenced, but results from different twin studies have varied. These studies also have demonstrated the important contribution of environmental risk factors. Some of the differences in findings may be caused partly by clinical heterogeneity, developmental differences in etiology (stronger genetic influences for depression symptom scores in adolescence than in childhood), and measurement issues, such as who rates the symptoms.