Patients with all stages of primary breast cancer are at continuing risk of relapse following 5 years of adjuvant tamoxifen therapy, even in the absence of lymph node involvement. Tamoxifen has been the standard therapy for reducing risk of recurrence, although more than 50% of relapses and deaths occur after completion of tamoxifen. Tamoxifen use is associated with an increased risk of serious side effects, and extended use beyond 5 years may have a negative impact on disease-free survival. Extended adjuvant letrozole therapy confers a significant benefit in relapse-free survival. The approval of letrozole for this indication in the USA and in many European countries introduces a new, safe and effective treatment for disease-free patients seeking to reduce their long-term risk of recurrence.