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Anti-estrogens are one of the classes of drugs used to treat ER+ breast cancer. Since their discovery they have been the drugs of choice in breast cancer treatment; prevention and adjuvant therapy for early breast cancer cases. Although anti-estrogens have been beneficial to a large number of patients, unfortunately about 40% of breast cancer patients and a majority of patients with metastatic breast disease who were initially responsive to the drugs will relapse and die of the disease. In spite of the current breakthrough in our knowledge of the molecular mechanisms that contribute to resistance, antiestrogen resistance remains a major setback in the treatment of ER+ breast cancer. In this review we examine the previously unexplored role of reactive oxygen species (ROS) and redox signaling in the molecular mechanism that contribute to breast cancer resistance to