Phytoestrogens are plant-derived compounds that can induce estrogenic effects in mammals. This chapter reviews the role of phytoestrogens, in particular the isoflavones from red clover and soy, as well as the prenylated flavonoids from hops, on human health. Red clover isoflavones are used as natural “safe” alternatives to hormone replacement therapy to help reduce menopausal symptoms and associated disease, such as osteoporosis. We review the current knowledge on the biological effects of various red clover isoflavones in vitro and in vivo, as well as the results from clinical trials. Soy is also a rich source of isoflavones, which is used in many food products, of particular focus in this chapter in infant formulas. We review the current knowledge on the biological effects induced by soy isoflavones in various rodent studies, and discuss the significance of such findings for human infant consumption. This chapter also highlights a more unique class of phytoestrogen, the prenylflavonoids, reviewing the in vitro and in vivo evidence for their estrogenic effects.