ABSTRACT Metastatic disease is the leading cause of death in cancer patients. Metastasis formation involves a cascade of events for which the underlying mechanisms are still poorly understood. During the metastatic cascade, cancer cells tightly interact with the immune system and they influence each other, both in the tumor microenvironment and systemically. The crosstalk between cancer and immune cells adds another layer of complexity to our understanding of metastasis formation, but at the same time opens new therapeutic opportunities for cancer patients. The intensifying development of immunotherapeutic strategies calls for a better understanding of immune regulation of metastasis in order to maximize the therapeutic benefit for patients with metastatic disease. In this Review and accompanying poster, we describe the main mechanisms of immune regulation of metastasis that have been reported to date, and present promising immunotherapeutic options that are currently available, or may become so in the near future, to tackle metastasis.