Idiopathic short stature (ISS) is a term used for children in whom the etiology of the short stature is undefined. Investigations of the growth hormone (GH)-insulin-like growth factor I axis have revealed several molecular and endocrinological defects in ISS patients. Abnormalities of GH secretion and action, although not frequent, will help to categorize some children with ISS. Because most diagnostic methods remain crude, however, their modification might be necessary to identify more subtle and yet functionally significant abnormalities of this endocrine axis.