A variety of therapeutic strategies are currently under investigation to inhibit factors that promote tumor invasion, as metastasis is the most common cause of mortality for cancer patients. Notably, considerable emphasis has been placed on studying metastasis as a dynamic process that is highly dependent on the tumor microenvironment. In regards to breast cancer, chemokine C-C motif ligand 5 (CCL5), which is produced by tumor-associated stromal cells, has been established as an important contributor to metastatic disease. This review summarizes recent discoveries uncovering the role of this chemokine in breast cancer metastasis, including conditions that increase the generation of CCL5 and effects induced by this signaling pathway. In particular, CCL-5-mediated cancer cell migration and invasion are discussed in the context of intertwined feedback loops between breast cancer cells and stromal cells. Moreover, the potential use of CCL5 and its receptor chemokine C-C motif receptor 5 (CCR5) as targets for preventing breast cancer metastasis is also reviewed.