Although significant advances have been made in the treatment of breast cancer using chemotherapy, less than half of the patients treated for localized breast cancer benefit from adjuvant chemotherapy and most patients with metastatic cancer eventually develop disease that is chemotherapy resistant. Targeted agents, such as inhibitors of tyrosine kinases, offer the opportunity to reverse chemotherapy resistance and enhance response in patients with localized and advanced breast cancer. Such combined approaches have been established for the treatment of advanced breast cancer and are now demonstrating benefit in the adjuvant arena. This review summarizes the results of several trials involving the use of tyrosine kinase inhibition in combination with chemotherapy for the treatment of breast cancer and discusses future directions for breast cancer biotherapy.