Glucocorticoids play an essential role in embryonic development and tissue homeostasis and possess important anti-inflammatory and immunosuppressive properties. Due to their very wide spectrum of activity, Glucocorticoids are one of the most commonly used drugs-used in the treatment of asthma, arthritis, autoimmune diseases and shock/SIRS. glucocorticoids are a main component of treatment regimens in hematological malignancies due to their pro-apoptotic properties and are also used as co-treatment several other cancers and chemotherapy regimens including those in breast cancer treatment. In breast cancer, however, glucocorticoids may have diverse effects and could inhibit chemosensitivity. Additionally, glucocorticoids through their receptor may interact with ER in a feedback loop regulating each other's activities. The normal variation of glucocorticoid levels with time of the day, menstrual cycle or year could have a interesting chronobiological interaction with the well recorded variation in breast cancer proliferation and metastatic potential. Glucocorticoids could play a very complex role in breast cancer epidemiology, biology and treatment; this review aims to present a comprehensive discussion as well as speculate future directions for research.