The administration of combination versus single-agent chemotherapy for the treatment of metastatic breast cancer remains an unresolved and controversial issue. Previous randomised trials have shown that, while combinations offer higher objective response rates, they have not always improved time to progression, quality of life or overall survival. Rationally designed combination regimens incorporating new cytotoxic and biological agents have resulted in improved survival rates compared with monotherapy and only modest increases in toxicities. However, trials analysing combination therapies lack formal cross-over arms and do not allow comparison of these regimens with sequentially administered single-agent therapy. This paper presents the latest randomised data and reviews the advantages and disadvantages of these two approaches to the treatment of metastatic breast cancer.