The idea of specific, targeted therapy is not a new one, and the treatment of breast cancer provides the oldest example of such a targeted therapy. More than 100 years ago, Beatson demonstrated that estrogen deprivation (by oophorectomy) caused regression of breast cancer. With the understanding of the mechanism of estrogen and estrogen receptor function, drugs that inhibit receptor activation or prevent the production of estrogen have been developed. Today, these hormonal strategies play a central role in the treatment of the majority of patients with breast cancer. This publication is devoted to therapies that take advantage of molecular targets relevant to breast cancer – so called novel molecular therapies. The chapters are meant to be a sampling of the different approaches being taken to improve upon the current treatment of breast cancer. It presents a sampling of both old and new molecularly targeted therapies that are being developed. They represent the beginning of an exciting new era in cancer treatment. However, each new, targeted therapy will need to be validated in preclinical and clinical testing. Furthermore, while the expression of a specific protein or activity of a particular pathway provides an indication of which specific therapy to use, it does not guarantee that therapy targeted to that pathway will be effective. Thus, a thorough understanding of the pathways served by the target and additional information about the molecular phenotype of each tumor will be necessary to truly select those tumors that are most likely to respond to molecularly targeted therapies.