During recent years, new advances in the field of estrogen signaling (e.g., the discovery of the second estrogen receptor named ERβ) have led to the conclusion that all the major human tissues are estrogen-responsive. The impact of estrogen on human health is far more complex and stronger than scientists had previously thought. Several scientists suggested that the interplay between ERα and ERβ (antagonism, synergism, etc.) simulates a Yin-Yang relationship. This article is intended to integrate the Yin-Yang theory of Traditional Chinese Medicine with modern scientific findings on estrogen signaling to offer a better understanding of the complex interactions between ERα and ERβ. A different approach, such as that of Yin-Yang theory, may complete the standard scientific perspective, reveal hidden meanings of the tissue-dependent ERα-ERβ predominance, and reveal new aspects of estrogen-receptor imbalance.