Depression pertains to the category of "Emotional Diseases" in traditional Chinese medicine (TCM). Its clinical symptoms are similar to the manifestations of "lily disease" from the TCM classics Synopsis of the Golden Chamber written by Zhang Zhongjing in the Han Dynasty. Also in this book, Lily Bulb and Rehmannia Decoction (LBRD) is the formula for the treatment of "lily disease". The classical herbal formula LBRD is composed of two herbs lily bulb and fresh rehmannia juice, with the function of nourishing yin and replenishing heart and lung. It has been clinically applied to treat "lily disease" for two thousand years. In this review, we focused on recent evidence linking LBRD and depression extracting data from animal and clinical studies, summarizing the primitive dosage and producing area of genuine medicinal materials of LBRD, clinical application, pharmacological mechanism and the effective substance basis for the treatment of depression. In conclusion, we discussed existing problems and future perspective. This systematic review will seek to enhance our understanding about pharmacology mechanism, herb-prescribing and recipe-constructing, and the development of novel formula for depression treatments.