Systemic adjuvant therapy reduces the mortality due to breast cancer to a modest extent. Current research directions focus on both increasing the efficacy of therapy, predominantly by increasing the intensity of treatment, and attempting to reduce toxicity by treating only those patients at significant risk of relapse. Improved understanding of both the metastatic process and the mechanisms by which cytotoxic treatments exert their effects hold the promise for more effective treatments in the future. Cost-benefit analyses demonstrate the relative cost-effectiveness of adjuvant systemic therapies for patients at significant risk of recurrence, for whom the effectiveness of treatment is substantial.