Outgrowths of disseminated metastases remain the primary cause of mortality in cancer patients; however, molecular and cellular mechanisms regulating metastatic spread remain largely elusive. Recent insights into these mechanisms have refined the seed and soil hypothesis and it is now recognized that metastasis of solid tumors requires collaborative interactions between malignant cells and a diverse assortment of “activated” stromal cells at both primary and secondary tumor locations. Specifically, persistent pro-tumor immune responses (inflammation), now generally accepted as potentiating primary tumor development, are also being recognized as mediators of cancer metastasis. Thus, novel anti-cancer therapeutic strategies targeting molecular and/or cellular mechanisms regulating these collaborative interactions may provide efficacious relief for metastatic disease. This review focuses on recent literature revealing new mechanisms whereby immune cells regulate metastatic progression, with a primary focus on breast cancer.