The occurrence of mood disorders is related to the dysfunction of the hypothalamic-pituitary-adrenal （HPA） axis. FK506-binding protein 5 （FKBP5）， a glucocorticoid receptor （GR） chaperone protein， regulates HPA axis function by regulating GR sensitivity. This article reviews FKBP5 gene and its application in drug therapy， electroconvulsive therapy， psychotherapy and FKBP5 antagonists in mood disorders.