The insulin-like growth factors are a family of growth factors, binding proteins and receptors that are involved in normal growth as well as in a number of pathological states. Overgrowth syndromes are a group of disorders characterized by a phenotype of excessive somatic and visceral growth. In addition, patients suffering from overgrowth syndromes are predisposed to develop cancer. Several specific defects linked to the insulin-like growth factor system were elucidated for a group of these disorders, including Simpson-Golabi-Behmel syndrome, Bannayan-Ruvalcaba-Riley syndrome and Beckwith-Wiedemann syndrome. The aim of this review is to examine recent data linking the phenotype of overgrowth syndromes, visceral growth and increased risk of neoplasia, with the molecular machinery of the IGF system.