Central nervous system (CNS) metastases is the most common type of brain malignancy, and breast cancer is the second most common type of malignancy to cause CNS metastases. Although the incidence of CNS metastases is less common than bone or visceral metastases, it is associated with poorer prognosis and is relatively unresponsive to systemic therapies. The incidence of CNS metastases in breast cancer has been estimated as 1-16% in clinical series, with higher rates (18-30%) in autopsy series. Recently a trend towards increasing CNS relapse has been noted, up to 25-34%. This may be partly explained by the increasing use of contrast-enhanced magnetic resonance imaging (MRI), heightened awareness by patient or clinicians, or an alteration in the natural history of breast cancer with improvements in systemic therapies, resulting in a prolongation of survival. Therefore, with improvements in treatments, metastases are better controlled, resulting in the CNS becoming a sanctuary for residual disease. The treatment of CNS metastases in breast cancer remains challenging. Surgical resection of tumor will prolong survival only in patients with a single lesion and with well controlled systemic disease. For patients with multiple lesions, whole brain radiotherapy (WBRT) remains the backbone in the management of CNS metastases. Recently the use of stereotactic radiosurgery alone or in combination with WBRT has been explored. Although better local control was achieved with the combination therapy, minimal overall survival benefit was seen. This may be secondary to the competing risk of death from systemic (extra-CNS) progression. The use of systemic agents including chemotherapy and hormonal therapy has been generally disappointing. This is often attributed to the impermeability of the blood-brain and blood-tumor barriers. Furthermore, P-glycoprotein (Pgp), a drug efflux pump encoded by the multidrug resistance gene, mdR1, is expressed in brain endothelial cells. Therefore, agents such as doxorubicin, cyclophosphamide, 5-fluorouracil, paclitaxel, docetaxel and vinorelbine, which are active against breast cancer, may either penetrate CNS poorly, or be transported out of the CNS environment. However, the blood brain barrier may be more leaky and permeable than previously thought in patients with CNS metastases, and these agents may achieve therapeutic concentrations in the CNS. As evidence for this, patients without prior exposure to agents such as cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and doxorubicin, can have significant objective responses in the CNS metastases. Today, most patients would have received these agents in the adjuvant setting, thus emphasizing the importance of both chemo-sensitivity together with CNS penetration, in the treatment of CNS metastases.