The recent discovery that an additional estrogen receptor (ER) subtype is present in various rat, mouse and human tissues has advanced our understanding of the mechanisms underlying estrogen signalling. The discovery of a second ER subtype (ERβ) suggests the existence of two previously unrecognised pathways of estrogen signalling: via the ERβ subtype in tissues exclusively expressing this subtype and via the formation of heterodimers in tissues expressing both ER subtypes. Various models have been suggested as explanations for the striking cell- and promoter-specific effects of estrogens and anti-estrogens, all on the basis of the assumption that only a single ER gene exists. This minireview describes several of these models and focuses on the potential role which the novel ERβ subtype might have in this regard.