In the vast majority of cases, cancer continues to be an incurable disease when it has spread beyond the primary organ. Most cancer research and therapy design to date has focused on chemotherapy directed at killing the replicating tumor cells. Little attention has been placed on targeting the microenvironments of the primary tumor site, the circulating tumor cells, or the metastatic or secondary (target) tumor site and how cancer cells move among them. To develop these targets, a better understanding of metastasis and the mechanisms underlying the spread of tumors is required. This review describes the steps of metastasis using a paradigm of emigration to migration to immigration, with prostate cancer as a model system.