From the early experience with tamoxifen to the current use of Herceptin, targeted therapy has been proven to be an important part of breast cancer (BC) treatment. In the last decade, advances in molecular biology have allowed scientists to design highly individualized, 'smart' pharmaceuticals, capable of manipulating the growth factor pathways and the genes that are involved in the development and maintenance of the malignant phenotype. The epidermal growth factor receptor (EGFR) family, as one of the best studied growth factor pathways in cancer, resembles a 'treasure island' by providing a wide range of biologically relevant targets involved in breast carcinogenesis. While a large number of new agents targeting this pathway are continuingly being tested in preclinical experiments, clinicians are witnessing the migration of some of these agents to daily practice. The aim of this review is to provide clinicians with an updated synopsis of the most advanced anti-erbB therapeutic strategies with activity against BC.