Twelve years of growth hormone (GH) therapy of short children born small for gestational age (SGA) have demonstrated that GH is an effective and well-tolerated therapy. Most children will reach a normal adult height (AH). AH of 55 SGA adolescents was comparable for those treated with a GH dose of 1 or 2 mg/m<sup>2</sup> (∼0.033 or 0.066 mg/kg) per day, mean (SD) AH SDS being –1.2 (0.7) and –0.8 (0.7), respectively. GH therapy had no influence on the age at onset, the progression of puberty, duration of puberty and pubertal height gain. GH therapy induced higher fasting and glucose-stimulated insulin levels after 1 and 6 years, but 6 months after GH stop, all levels returned to normal. At baseline mean systolic blood pressure was significantly increased, but both systolic and diastolic blood pressure decreased significantly during 6 years of GH and remained so after GH stop. GH therapy demonstrated a beneficial effect on serum lipid profiles, body composition, bone mineral density and head growth. Treatment with 2 mg GH/m<sup>2</sup> per day induced mean serum IGF-I levels of +2 SDS, whereas IGF-I levels remained within the normal range with 1 mg GH/m<sup>2</sup> per day. In conclusion, long-term GH therapy of short SGA children with 1 mg/m<sup>2</sup> per day appears to be effective and safe. Since the future consequences of high serum IGF-I levels during long-term GH therapy with 2 mg/m<sup>2</sup> per day are as yet unknown, it seems safer to treat short prepubertal SGA children with a GH dose of 1 mg/m<sup>2</sup> per day when children are to be treated continuously for many years.