Growth hormone (GH) therapy has evolved rapidly over the past decade. Ongoing research has demonstrated a clear role for therapeutic GH in a wide spectrum of pediatric disorders involving both poor growth and abnormal body composition. Although guidelines for GH dosing are not fully established, a series of key studies has delineated the range of dosages that are useful in the treatment of children with growth disorders. The recent approval of idiopathic short stature (ISS) as an indication for GH therapy presents further challenges in optimizing the care of GH-treated patients. ISS is now recognized as a diverse collection of environmental and molecular abnormalities, some of which involve the GH-IGF axis. Emerging data indicate that serum IGF-I measurements are not only useful in the diagnosis of growth abnormalities but, in conjunction with auxological measurements, are also a powerful tool for assessing GH efficacy. While it is clear that many ISS patients respond to GH, some individuals will not show a satisfactory response. Monitoring IGF-I levels and change in height SDS during treatment can assist the physician in distinguishing those patients in whom GH successfully and safely induces statural growth from those with partial or complete GH insensitivity who might benefit from modified GH treatment protocols or alternate therapies. In addition, serum IGF-I measurements are increasingly used as part of a rational monitoring strategy to ensure safety of GH dosing in light of cumulative data associating high IGF-I levels with potential malignancy risk, and low IGF-I levels with cardiovascular disease risk.