Estrogens along with their receptors are required for the normal physiological development of women. However, in altered physiological conditions a high level of estrogens acts either as initiator or progressor of breast cancer. Approximately in 75% of estrogen dependent breast cancer cases estrogen receptors (ERs) are held responsible. Recent studies indicate that estrogens along with iron (Fe) concomitantly involved in the proliferation of ER(+) breast cancer cells. While a number of antiestrogen/anti-ER drugs including selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and selective estrogen receptor down regulators (SERDs) are used to eradicate breast cancer but their action on Fe dependent breast cancer complication is not yet explored. Moreover, many of the ER(+) breast cancer patients receiving anti-estrogen drugs relapsed within a couple of years and become resistant to antiestrogen therapy. Mutation and loss of affinity to the target molecule (ERs), loss or overexpression of ERs, along with activation of growth promoting pathways alternative to estrogen-ER pathways are the major reasons of drug resistance. Combinational therapy may be best alternative to antiestrogen relapsed patients. Some of the widely studied drug combinations are roscovitine (ROSC) and tamoxifen, metformin and tamoxifen, tamoxifen and RAD001. While in all these drug combinations anti-ER compound tamoxifen may be one of the major content, anti-Fe compounds are yet to be used as drug combination. The present review article describes all the currently studied drugs/drug combinations in ER(+) breast cancer cells and future drug possibilities including anti-Fe compounds.