Selective estrogen receptor modulators (SERMs) have offered the promise of reducing the burden of coronary artery disease (CAD) in postmenopausal women, based on the positive effects recorded on intermediate markers (blood lipids and markers of inflammation). The effects of raloxifene, bazedoxifene and lasofoxifene on cardiovascular endpoint markers are presented as reported in recent, randomized, controlled trials. Raloxifene failed to significantly lower the risk of CAD in postmenopausal osteoporotic women, without any effect on stroke or early harm, but doubling the risk of venous thromboembolism. The risk of CAD was lowered in a subgroup of patients at risk of CAD. In a large randomized, controlled trial with CAD as the primary endpoint in patients at risk of CAD, raloxifene failed to significantly reduce CAD, while significantly increasing the incidence of fatal stroke and venous thromboembolism. Bazedoxifene, in an osteoporosis trial, had similar effects on the cardiovascular system when compared to raloxifene. Lasofoxifene has only been studied in postmenopausal osteoporotic women in the PEARL trial. Lasofoxifene reduced the risk of coronary heart disease events as well as the risk of stroke, while the risk of deep vein thrombosis remained in line with other SERMs. These results will need to be confirmed in a study with primary cardiovascular endpoints. Until then, it is unlikely that SERMs will play a major role in strategies aimed at the prevention of coronary heart disease in postmenopausal women.