Increasing use of standard chemotherapy, especially anthracycline- and taxane-based therapies, in early-stage breast cancer has led to a corresponding increase in heavily pretreated and/or treatment-resistant cases of metastatic breast cancer (MBC). Thus, second and later lines of MBC therapy frequently involve the clinically challenging picture of progressive disease and limited treatment options. While several prognostic factors have been identified to aid treatment selection in MBC patients, treatment is palliative and aimed at prolonging survival, controlling symptoms, and maximizing patients' quality of life. No globally accepted standard exists for meeting these goals, and treatment patterns vary according to region. The list of available agents for the treatment of MBC is increasing with newer chemotherapeutic agents and molecular-targeted therapies. Within recent years, several single-agent and combination chemotherapy regimens have been shown to improve progression-free survival and reduce symptoms of disease in clinical studies in patients with resistant and/or heavily pretreated MBC. However, at present, the demonstrated benefits of these medical interventions have usually not included extension of overall survival times. It is hoped that in the near future, ongoing refinements to treatment approaches used in second-line settings and beyond will allow meaningful improvements in symptom control and survival in MBC.