Estrogens are primarily identified as sex hormones that, for a long time, have been known as important regulators of female reproductive physiology. However, our understanding of the role of estrogens has changed over the past years. It is now well accepted that estrogens are also involved in other physiological and pathological processes in both genders. This is due to the fact that estrogen can act both local as well as on a systemic level. Next to its role in reproductive physiology, there is accumulating evidence that estrogen influences multiple systems involved in water homeostasis. This chapter will delineate the regulatory effects of estrogen on the water channel aquaporin-2 (AQP2) found in the renal collecting duct. We will first provide an introduction to estrogen, the estrogen receptors and their role in renal physiology as well as describe the effect of selective estrogen receptor modulators (SERMs) on the kidney. Subsequently, we will focus on how estrogen and SERMs influence water balance and regulate AQP2 expression in principal cells of the collecting duct. Finally, we will describe how estrogen regulates AQP2 functionality in other organ systems.