Longitudinal bone growth occurs in the growth plate through a process where resting zone chondrocytes are recruited to start active proliferation and then undergo differentiation, followed by apoptosis and later mineralization. Bone growth is controlled by several hormones and growth factors acting systemically and/or locally in the growth plate. From studies of individuals with aromatase deficiency and a man with defective estrogen receptor (ER)-alpha it has become clear that estrogen action is indispensable for normal pubertal growth and growth plate fusion. Any functional role of ERbeta has not yet been defined in the human growth plate. As new specific modulators of estrogen receptors are developed, these could offer more specific ways to modulate longitudinal growth and growth plate fusion. It is difficult to extrapolate data obtained in experimental animals, as clear species differences exist, emphasizing the need for new models allowing studies in human growth plate cartilage.