Retinoids comprise both naturally and synthetically occurring compounds that have been proven to be differentiation agents for a variety of neoplasias, including breast cancer and promyelocytic leukemia in animal models and humans. They offer a unique panoply of therapeutics for the prevention or treatment of breast cancer. Nonetheless, considerable controversy remains as to the efficacy and potential toxic side-effects and as to which group of patients may most benefit. In this article, we review evidence of retinoid efficacy in breast cancer in humans and in animal models and provide possible mechanisms of retinoid action in breast cancer treatment, focusing on the roles of the different retinoic acid receptors and the metabolic pathways necessary for gene activation and cellular homeostasis.