With the availability of recombinant human (rh) IGF-I as a new therapeutic agent, the criteria for diagnosis and strategies for management of growth deficiencies continue to evolve. This supplement provides a clinical update on molecular, therapeutic, and metabolic aspects of the management of short stature associated with insulin-like growth factor-I deficiency (IGFD). Several distinct, single-gene defects associated with primary IGFD now have been identified. The first section of this supplement focuses on selecting certain patients for specific genetic testing of the GH/IGF-I axis, based on previously obtained clinical and biochemical assessments. Management of short stature in children responding poorly to rhGH and definitions of a good and poor response are discussed in the next section. In addition, the authors further address different methods to help practicing clinicians predict and assess GH response, review the effect of rhGH on final adult height, and discuss the role IGF-I may have in the therapeutic approach to short stature. Finally, the metabolic aspects related to the treatment of short stature are discussed in the third part of this supplement.