In Western countries, breast cancer is the most common cancer in women but available interventions can reduce risk. The aim of the paper was to review the available evidence regarding breast cancer chemoprevention trials. A systematic literature search was conducted to identify all full‑scale, randomized prospective chemoprevention trials as well as similarly conducted randomized trials with breast cancer as the primary monitoring endpoint. In full‑scale, randomized chemoprevention trials, the selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, reduce breast cancer incidence. In a direct comparison, tamoxifen resulted in greater breast cancer reduction than raloxifene but with greater endometrial cancer risk. The aromatase inhibitors, exemestane and anastrozole, also reduce breast cancer incidence in breast cancer prevention trials. In the Women's Health Initiative hormone therapy trials, in postmenopausal women with no prior hysterectomy, estrogen plus progestin increased breast cancer incidence and deaths from breast cancer, while estrogen alone, in women with prior hysterectomy, reduced breast cancer incidence and reduced deaths from breast cancer. For premenopausal women at increased breast cancer risk, tamoxifen is a proven option with favorable side effect profile. For postmenopausal women, while no direct comparison of SERMs and aromatase inhibitors for chemoprevention are available, cross‑study comparisons suggest greater efficacy and more favorable side effect profile for aromatase inhibitor use, especially for older women. The opposite effects of estrogen plus progestin compared with estrogen alone on breast cancer incidence and outcome should factor into risk‑benefit consideration when these agents are considered for climacteric symptom management.