Clinical trial data on selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) have demonstrated reduced breast cancer incidence in the prevention setting among high-risk women. We conducted an extensive review of clinical trials and recent published reports of barriers to uptake of breast cancer chemoprevention, to provide health care professionals with information to improve decision-making regarding chemoprevention. Despite the positive results of these trials, uptake of chemoprevention has been low due to barriers in identifying high-risk women, lack of understanding of risks and benefits, as well as concerns about side effects. Interventions designed to increase uptake have met with limited success. Clinicians can support women in informed decision-making about SERMs and AIs by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of chemoprevention. Promoting uptake and adherence to chemoprevention holds promise for reducing the public health burden of this disease.