Resistance to chemotherapy is a major obstacle to the effective treatment of many tumor types. Although many anticancer therapies can alter tumor growth, in most cases the effect is not long lasting. Consequently, there is a significant need for new agents with low susceptibility to common drug resistance mechanisms in order to improve response rates and potentially extend survival. Approximately 30% of the women diagnosed with early-stage disease in turn progress to metastatic breast cancer, for which therapeutic options are limited. Current recommendations for first-line chemotherapy include anthracycline-based regimens and taxanes (paclitaxel and docetaxel). They typically give response rates of 30 to 70% but the responses are often not durable, with a time to progression of 6 to 10 months. Patients with progression or resistance may be administered capecitabine, gemcitabine, vinorelbine, albumin-bound paclitaxel, or ixabepilone, while other drugs are being evaluated. Response rates in this setting tend to be low (20 to 30%); the median duration of responses is <6 months and the results do not always translate into improved long-term outcomes. The present article reviews treatment options in taxane-resistant metastatic breast cancer and the role of ixabepilone in this setting.