Results of clinical trials over the past 15 years demonstrate that the taxanes are among the most effective new class of cytotoxic drugs to treat breast cancer and other solid tumors. Moreover, the efficacy of the taxanes added further credence to the relevance of the microtubule as a tumor target. In spite of the significant benefits observed in early and advanced breast cancer, a number of factors contribute to disease relapse and, perhaps more discouragingly, disease refractoriness. After exhausting cytotoxic chemotherapy, hormonal therapy, and other molecular-based-therapies, patients whose tumors exhibit taxane resistance had virtually no additional options. This paper, a product of the ongoing advances in the treatment of breast cancer, reviews two important areas: first, molecular concepts and relevance of the microtubule in breast cancer and second, clinical implications of ixabepilone, a novel, nontaxane tubulin-stabilizing agent in patients with taxane-resistant breast cancer.