Adjuvant chemotherapy improves survival for patients with early-stage disease but this benefit is not equal for all patients. Molecular characteristics of the cancer affect sensitivity to chemotherapy. In general, estrogen receptor (ER)-negative disease is more sensitive to chemotherapy than ER-positive tumors. Before any new molecular classification (or predictive test) is adopted for routine clinical use, however, several criteria need to be met. This review describes the current limitations and future promises of gene-expression-based molecular classification of breast cancer and how it might impact selection of adjuvant therapy for individual patients.