Breast cancer is a heterogeneous disease, encompassing several histological types and clinical behaviors. Current histopathological classification systems are based on descriptive entities with prognostic significance. Few prognostic and predictive markers beyond those offered by histopathological analysis are available. High-throughput molecular technologies are reshaping our understanding of breast cancer, of which microarray-based gene expression has received most attention. This method has been used to derive a molecular taxonomy for breast cancer, which has provided interesting insights into the biology of the disease. Class prediction studies have generated a multitude of prognostic/predictive signatures, which herald the promise for an improvement in treatment decision making. However, most of the signatures developed to date seem to have discriminatory power almost restricted to estrogen receptor-positive disease. This review addresses the contribution of gene expression profiling to our understanding of breast cancer and its clinical management.