Inflammatory breast cancer is rare but represents the most aggressive and lethal form of locally advanced breast cancer. The management of inflammatory breast cancer has evolved substantially over the last 40 years; current multimodality therapy regimens combine chemotherapy, surgery, and radiation. While identification of the optimal combination of these traditional therapies remains a goal, novel targeted therapies that have recently become available promise improved responses and survival. In this review, we discuss some recent developments in the use of systemic therapies for inflammatory breast cancer.