So far, the clinical evaluation of short children has focused on the measurement of immunoreactive growth hormone (GH) in the blood to determine if the growth retardation is due to GH deficiency. However, GH-dependent short stature may be caused by defects in either the secretion of bioactive GH or by the inability to respond to GH. Both GH secretion and GH responsiveness should, therefore, be evaluated when investigating the cause of short stature. Recent advances in molecular biology have generated new ways of studying different molecules involved in growth regulation, and new genetic defects have been identified in short children.