The advent of multimodality therapy for patients with inflammatory breast cancer (IBC), consisting of neoadjuvant chemotherapy, particularly taxanes, surgery, radiotherapy, and hormonal therapy, has improved survival. A pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer and IBC improves outcomes, which suggests that obtaining a pathologic complete response to neoadjuvant chemotherapy has prognostic significance. The benefit of high-dose chemotherapy has shown encouraging results; however, this approach needs to be prospectively evaluated and to date remains experimental. Vascular endothelial growth factor, a promoter of angiogenesis, is highly expressed in IBC, making the angiogenesis pathway an attractive therapeutic target. A better understanding of the complex biology of IBC is needed for the development of additional targeted agents to further improve outcomes for patients with this aggressive form of breast cancer. Cancer 2010;116(11 suppl):2821–8. © 2010 American Cancer Society.