Abstract Breast cancer is the most frequently diagnosed cancer in women and 70% of the cases are hormone-dependent. The presence of ERα is one of the most important prognostic factors predictive of response to endocrine therapy in human breast cancers. Resistance to endocrine therapies has become a major public health concern and it appears essential to understand the mechanisms underlying this phenomenon. This review provides insights into the molecular mechanisms associated with resistance to endocrine therapies and presents the different strategies currently developed in pre-clinical models to overcome this resistance.