The use of gene expression profiling has impacted our understanding of breast cancer biology and increasingly has played a role in guiding clinical decisions. We have used hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status for years to guide selection of therapy. More recently, gene expression analysis has facilitated the identification of at least five intrinsic subtypes of breast cancer. Potential therapeutic targets have also been identified using genomic profiling. Several tests, such as the 21-gene recurrence score assay (Oncotype DX) and the 70-gene prognosis signature (MammaPrint), have been well validated as prognostic tools for early-stage breast cancer, and have aided in adjuvant therapy decisions for early-stage, HR-positive breast cancer patients. Genomic profiling has the potential to provide additional insight into drug discovery and clinical trial design by identifying appropriate targeted therapies for subtypes of breast cancer.