Acromegaly is a disease of exaggerated somatic growth and distorted proportion arising from hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although almost never malignant, somatotropinomas may cause significant morbidity and the uncontrolled excess of GH is related to mortality 2 to 4 times higher than the expected rate. Recently, clinicians treating acromegalic patients have been aware of the importance of trying to normalize IGF-1 while GH values may differ depending on assay. Despite the significant efforts made over the last decade, little is known about the genetic causes of somatotropinomas and even less of this knowledge is applied therapeutically. In this review, we attempt to address the genetic and molecular knowledge regarding somatotropinomas and their therapeutic aspects.