Context.-Despite advances in breast cancer management, women continue to relapse and die of breast cancer. Traditionally, evaluation for hormone receptors (estrogen and progesterone), as well as HER2 overexpression, have guided therapy-related decision-making because they are both prognostic and predictive indicators. However, there are limitations with those studies, which can lead to improper treatment. Gene signatures have recently been shown to be of value in identifying molecular portraits of breast carcinoma and are beginning to play role in management and treatment algorithms. Objective.-To provide a summary of the prognostic and predictive indicators of breast cancer, such as hormone receptors, HER2, and molecular gene signatures that currently help guide clinical decision making. Data Sources.-Published articles from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusions.-Emerging evidence shows promise that, in addition to hormone receptors and HER2 studies, evaluating tumors with gene expression profiling can provide additional prognostic and predictive information, further aiding clinical management and leading to a more personalized approach to treating breast cancer.