The major cause of death from cancer is the relentless growth of metastases that are resistant to conventional therapy. The pathogenesis of a metastasis is complex and requires that tumor cells complete a sequence of potentially lethal interactions with various host factors. The finding in 1973 that metastasis is a selective process and the finding in 1977 that malignant neoplasms are heterogeneous and contain few preexisting metastatic subpopulations have added a new dimension to our understanding of cancer and its spread. This understanding is now contributing to the design of better therapies against disseminated metastasis.