Estrogens control a variety of physiological and disease-linked processes, most notably reproduction, bone remodeling and breast cancer, and their effects are transduced through classic nuclear receptors referred to as estrogen receptor-α (ERα) and ERβ. Recent results obtained using the estrogen-related receptors (ERRα, -β and -γ), a subfamily of orphan nuclear receptors closely related to the ERs, have shown that the ERRs share target genes, coregulatory proteins, ligands and sites of action with the ERs. In addition, the ERRs can actively influence the estrogenic response, suggesting that pharmacological modulation of ERR activity will be clinically useful to prevent and/or treat a variety of conditions related to women's health.