Adjuvant chemotherapy improves survival of patients with stage I-III breast cancer but it is being increasingly recognized that the benefit is not equal for all patients. Molecular characteristics of the cancer affect sensitivity to chemotherapy. In general, estrogen-receptor-negative disease is more sensitive to chemotherapy than estrogren-receptor-positive disease. Large-scale genomic analyses of breast cancer suggest that further molecular subsets may exist within the categories defined by hormone receptor status. It is hoped that the new molecular classification schemes might improve patient selection for therapy. Before any new molecular classification (or predictive test) is adopted for routine clinical use, however, several criteria need to be met. There must be an agreed and reproducible method by which to assign molecular class to a new case. Cancers that belong to different molecular classes must show differences in disease outcome and treatment efficacy that affect management and treatment selection. Also desirable are results from prospective clinical trials that demonstrate improved patient outcome when the new test is used in decision-making, compared with the current standard of care. This Review describes the current limitations and future promises of gene-expression-based molecular classification of breast cancer and how it might impact on selection of adjuvant therapy for individual patients.