Postmenopausal estrogen replacement, with or without progestin therapy, has a generally favorable impact on lipids, improves endothelial function, and has anti-inflammatory and antioxidant effects. These properties should favorably impact coronary risk; indeed, epidemiologic studies have consistently associated hormone replacement therapy with reduced coronary risk. Nonetheless, the Heart & Estrogen/progestin Replacement Study (HERS), a randomized, placebo-controlled, secondary prevention trial of conjugated estrogen with progestin, found no overall reduction in coronary events among women assigned to active hormone treatment. This review explores the role of estrogen replacement among interventions intended to prevent coronary heart disease in the post-HERS era.