Cytotoxic chemotherapy is important for treatment of patients with hormone-insensitive advanced breast cancer. A variety of new cytotoxic agents are promising alone or in combination. The originality, the clinical activity and side effects, as well as the current development status of these agents are reviewed. These agents include the new antimicrotubules (analogues of taxanes and vinorelbine; epothilone derivatives), oral formulations of 5-fluorouracil and other antimetabolites (tomudex, alimta, gemcitabine), liposomal anthracyclines, platinum analogues, topoisomerase I inhibitors and other compounds such as ET-743. Finally, new molecular-targeted therapies of potential interest in the treatment of metastatic breast cancer are reviewed. The growing availability of such biological therapies given alone and mainly in combination with hormonal and chemotherapeutic agents may improve in the near future the outcome of patients with metastatic breast cancer.