The roles of androgen and estrogen in pubertal growth, epiphyseal maturation, and accretion of bone mass have generally been perceived to be overlapping. Described in this article are three recently published novel case reports that reveal important new concepts regarding the relative roles of these two classes of hormones. A woman and a man with aromatase deficiency and a man with estrogen resistance secondary to an estrogen-receptor mutation are described. The details of their phenotypes reveal that although androgens have direct growth-stimulating actions on the epiphysis, the final phase of skeletal maturation associated with epiphyseal closure seems to be primarily an estrogen-dependent phenomenon in men and women. In addition, bone mass accrued during puberty is primarily induced by estrogen in both sexes.