While traditionally recognized as a sex hormone, estrogen has a potent effect on the development of tissues beyond those of the reproductive system. Estrogen synthesis enzymes and estrogen receptors are broadly expressed in vertebrate tissues, further indicating their importance in various processes. These include the tissues of the zebrafish, which is a particularly suitable model for studying early development due to its rapid ex utero ontogeny and conserved genetic and cellular composition with other vertebrates. In this review, we provide readers with an overview of estrogen signaling, discuss important attributes of the zebrafish animal model with a special focus on the kidney, and explore recent insights from zebrafish studies about the roles of estrogen signaling in organogenesis across germ layer derivatives that range from the kidney to the brain and liver.