Background: Acromegaly is a growth disorder, but mostly it is a metabolic disease related to excessive production of growth hormone (GH). It is characterized by progressive somatic disfigurement in combination with sometimes severe systemic manifestations. Long-acting somatostatin analog (SSA) therapy normalizes serum insulin-like growth factor I (IGF-I) levels in approximately 55% of patients, but we postulate that these patients still have acromegaly in many tissues other than the liver. Direct and indirect effects of SSA reduce hepatic IGF-I generation and make the liver behave as if it is GH resistant. The remaining 'peripheral' or non-hepatic acromegaly has a significant negative impact on the quality of life of these patients. Conclusions: Pegvisomant is the most effective medical treatment for acromegaly. Due to its mode of action and pharmacodynamic properties, it is the ideal partner for combination therapy with an SSA for acromegalic patients with a remaining, peripheral form of the disease.