In a short period of time DNA microarray technology has revolutionized our understanding of human cancer biology. This has been particularly impressive in the field of breast cancer research, where the clinical heterogeneity long observed by physicians seems to be mirrored by different molecular phenotypes exposed by microarray analysis. Gene-expression signatures have been developed to predict prognosis and treatment response and pending adequate validation, are on the verge of entry into the clinical setting. In this review article we explore how gene-expression profiling has influenced our understanding of the ER-positive breast cancers: that proliferation and cell-cycle genes seem to be the strongest predictor for metastasis and relapse in this group, and discuss the various gene predictors and molecular subtype classifications that exist that may help us individualize therapy for these women.