The use of systemic (drug) therapy postoperatively reduces the risk of relapse and death for patients with resectable invasive breast cancer. The Early Breast Cancer Trialists' Collaborative Group overview analysis confirmed the benefits of both polychemotherapy and tamoxifen in broad subgroups of patients. It remains a challenge, however, to quantify the risk of relapse and the benefit of therapy for individual patients. If the ipsilateral lymph nodes are free of metastases and the tumor is infiltrating ductal or lobular in histology and less than 1 cm in diameter, the risk of relapse is low, so the benefits of standard treatments are too small to warrant routine use. For node-negative patients with larger tumors or for those with positive lymph nodes, the benefits of therapy are significant, although many of these individual patients will not relapse. Hence, better prognostic methods, improving the accuracy of predicting an individual patient's risk, could allow for more rational treatment recommendations. The most widely used polychemotherapy combination incorporates three drugs: cyclophosphamide, methotrexate, and fluorouracil. The substitution or inclusion of doxorubicin, which is somewhat more toxic than the cyclophosphamide, methotrexate, and fluorouracil regimen, is justifiable in subsets of patients at higher risk of relapse, eg, those with metastatic involvement of four or more axillary lymph nodes. Because higher dose intensity (the amount of drug given per unit time) of chemotherapy improves relapse-free survival, phase II clinical trials are testing various dose-intensification strategies, and phase III trials are underway to determine their comparative efficacy. Tamoxifen is now the standard hormone therapy. It is routinely offered to many patients older than the age of 50 years because it is more active in a low-estrogen environment. In these patients, tamoxifen produces benefits additive to those of chemotherapy. In younger women and in those whose tumors do not express hormone receptors for estrogen or progesterone, tamoxifen is less effective. New directions for adjuvant therapy include the incorporation of new chemotherapy agents (ie, paclitaxel), novel modalities (ie, monoclonal antibodies or vaccines), and possibly dietary interventions.