Antineoplastic therapies can be classified as either cytotoxic systemic chemotherapy or targeted biological therapy. In many ways, cytotoxic chemotherapy is "targeted" at specific molecules that regulate progression through the cell cycle; however, these targets are generally not specific for tumor cells. Because systemic cytotoxic chemotherapy targets all rapidly dividing cells, it also attacks hair follicles, gastrointestinal mucosa, and hematopoietic cells thereby inducing the classical side effects of treatment such as alopecia, nausea, diarrhea, mucositis, and bone marrow suppression. The newer generation of targeted biological therapies is still administered systemically as traditional chemotherapy; however, these drugs are unique in that they are designed to target specific molecular components in tumor cell biology with the hope of minimizing cytotoxicity to noncancerous cells. In addition, they have toxicities specific to their mechanism of action. This chapter provides an overview of the biology of systemic therapy for breast cancer.