There is a broad spectrum of organ systems that respond to estrogen hormones, including the female and male reproductive tracts, mammary gland, the skeleton, cardiovascular system and central nervous system. The physiological effects of estrogens are mediated by the estrogen receptor, a member of the nuclear receptor superfamily of transcription factors. Two estrogen receptors have been identified: the originally described estrogen receptor alpha (ERalpha) and the more recently discovered estrogen receptor beta (ERbeta). Three different estrogen receptor knockout (ERKO) mouse models were generated, carrying a null mutation in the ERalpha gene (alphaERKO), the ERbeta gene (betaERKO) or both genes (alphabetaERKO). The generation of the different ERKO mice provides ideal models for studying the physiological consequences of the complete lack of estrogen receptor activity and the distinct roles of both estrogen receptors in various tissues. This review summarizes the phenotypes principally seen in the female reproductive system of the different ERKO mice.