The promising activity of taxanes in advanced breast cancer patients has prompted the investigators to explore their role in the adjuvant setting. Methodological issues, still unsolved pharmacokinetic and pharmacodynamic problems, and potential severe toxicities could jeopardize these attractive regimens and should be taken into account in the design and interpretation of adjuvant trials. In order to minimize the methodological drawbacks, the potential role of taxanes in the adjuvant setting should be assessed in clinical trials powered to detect an absolute survival increase of near 7% at 10 years. The use of paclitaxel in combination with anthracyclines is complicated by pharmacokinetic interactions which may be responsible for unexpected side effects and/or subadditive cytotoxicity. Moreover, possible interactions between taxanes and tamoxifen are still unclear, and therefore more data are necessary before recommending the combined use of the two drugs in the adjuvant setting. Nowadays, the majority of breast cancer patients receive conservative surgery followed by radiotherapy; when adjuvant taxanes are used, radiotherapy should be delayed because of their radiosensitization effect, with potential detrimental effects. Finally, the majority of side effects of taxane-containing regimens are short-lasting and reversible, but other potential toxicities, such as the cardiotoxicity and long-term possible sequelae of the use of high-dose steroids, need long-term evaluation.