Changes in clinical practice regarding favoured first-line and adjuvant treatments for postmenopausal women with advanced breast cancer (ABC) mean that it is becoming increasingly important to identify agents that are effective following aromatase inhibitor (AI) failure as well as tamoxifen failure. Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that binds, blocks and degrades the ER. Fulvestrant is at least as effective as anastrozole following tamoxifen failure and also shows activity after progression on AIs. Its very good tolerability profile and novel mode of action, might offer potential for the use of fulvestrant in combination regimens, and there is also scope for investigating the use of loading and higher dose regimens in an attempt to further enhance efficacy. Here, the rationale and evidence for the efficacy of fulvestrant following AI failure and its combination with AIs and novel agents such as gefitinib and trastuzumab will be reviewed. The ongoing clinical development programme for fulvestrant will more fully the role of this valuable new agent in the treatment of postmenopausal ABC.