The recent studies on humans with a defective gene that encodes aromatase p450 (p450arom) and aromatase knockout (ArKO) mice with a disrupted p450arom gene uncovered many interesting aspects of physiology. Aromatase-deficient humans and ArKO mice continue to serve as invaluable models for us to study the roles of estrogen in normal and abnormal functions of several tissues. These roles will be discussed in detail in the following review article.