Despite progress in combined-modality treatment with chemotherapy, surgery, and radiation therapy, the long-term outcome for patients with inflammatory breast cancer (IBC) remains poor. Therapies that target vasculolymphatic processes--angiogenesis, lymphangiogenesis, and vasculogenesis--have shown potential in the treatment for IBC, as represented by bevacizumab. Although the therapeutic effect of targeting lymphangiogenesis and vasculogenesis requires further investigation, targeting of angiogenesis has potential, not only through true antiangiogenic effects, but also through antitumor effects in concert with other pathways. Therapies that target cell proliferation pathways are the most promising targeted therapies for IBC. In particular, therapies that target human epidermal growth factor receptor 2 (for example, trastuzumab and lapatinib) have performed well in the clinical setting, leading to improved outcomes for patients with IBC. Metastatic pathways could have a unique, key role in the aggressiveness of the IBC phenotype. Further extensive work on the unique molecular characteristics of IBC is essential to ensure improved outcomes for patients with this disease. In this Review we discuss three pathways--vasculolymphatic, cell proliferation and metastatic--that could represent important targets in the treatment of IBC.