Over 12 years' experience with recombinant human growth hormone (rhGH) treatment has created a powerful and safe therapeutic tool. However, to fully optimize the potential of GH therapy and to provide a guide for future GH research, several key issues must be addressed. These are the identification of specific patients or conditions for whom rhGH provides proven long-term benefit; an understanding of when treatment should be started and stopped; a determination of the best dose and regimen; establishment of the most accurate parameter in measuring success of the treatment plan; and recognition of the therapy's potential adverse effects and their relation to dosing. To date, approved pediatric indications for GH therapy are GH deficiency, chronic renal insufficiency and Turner syndrome. Long-term benefits for other indications have yet to be clearly demonstrated. Although starting GH therapy at the youngest possible age yields better results, the treatment endpoint remains controversial. Data so far has shown that daily injections are superior to thrice weekly dosing. Bedtime administration provides more physiologic GH profiles than morning injections. Subcutaneous administration of GH is as efficacious as intramuscular GH and better tolerated. Published pilot studies and large ongoing pediatric trials suggest that the growth response is dose-dependent between 0.025 and 0.1 mg/kg per day. Studies in adults, however, show efficacy at lower doses. It appears that both auxologic and biochemical parameters are useful in assessing treatment efficacy, but which marker is best suited for indicating appropriate dose adjustments remains unclear. The normalization of serum GH-dependent growth factors may have a role in individualizing the GH dose in a similar way to the approach used in managing other endocrine deficiencies.