Although endocrine therapy is highly effective in the treatment of endocrine receptor-positive breast cancer, chemotherapy has been shown to provide clinical benefit when added to tamoxifen. However, baseline risk after tamoxifen treatment is so low, especially in patients who are axillary node negative, that significant overtreatment will result if chemotherapy is given to every patient. Robust prognostic and predictive markers need to be developed to identify those at high risk of treatment failure. Although comprehensive gene expression profiling methods do offer promise, they require fresh or frozen tumor samples. To take advantage of existing archived tissue blocks with clinical follow-up collected from finished clinical trials, such as National Surgical Adjuvant Breast and Bowel Project trials B-20 and B-14, technologies that allow interrogation of archived blocks for gene expression profiling need to be realized. Recent developments in gene expression profiling technologies are discussed with their implications in clinical management of endocrine receptor-positive breast cancer.