Adjuvant chemotherapy reduces the risk of relapse and mortality for women with early-stage breast cancer. However, many women diagnosed with early-stage breast cancer experience the toxic effects associated with adjuvant chemotherapy without any meaningful benefit. There are a variety of clinicopathological factors--including hormone receptor expression, histology, and proliferation markers such as Ki-67--that can be used to try to identify patients who can safely avoid adjuvant chemotherapy. In addition, novel molecular tools, including the intrinsic molecular subtypes, prognostic multigene assays, and levels of urokinase-type plasminogen activator, provide further prognostic and predictive information to the standard clinicopathological factors thereby improving the accuracy of risk-of-relapse estimation and of the likelihood of response to cytotoxic chemotherapy.