Although tamoxifen has been an effective treatment for breast cancer, several novel anti-oestrogen compounds have been developed with a reduced agonist profile on breast and gynaecological tissues. These include selective oestrogen receptor modulators (SERMs; both 'tamoxifen-like' and 'fixed-ring' SERMs) and selective oestrogen receptor downregulators (SERDs), although none has been proved superior in efficacy to tamoxifen in various advanced breast cancer trials. Thus, many have questioned whether a need for SERMs in breast cancer still exists, although chemoprevention remains a possible niche setting. In contrast, SERDs may have useful efficacy following aromatase inhibitors because of their unique mechanism of action, and clinical trials to determine their optimal use or sequence are ongoing.