Metastasis is the main cause of cancer-related mortality yet there are no therapies that specifically target metastatic disease. Current chemotherapies target the primary tumor but are also cytotoxic to normal proliferating cells in the body, limiting treatment efficacy. To find metastatis-specific treatments we need to identify and target specific vulnerabilities of metastasizing cancer cells. Historically studies have focused on the molecular biology of the early steps of transformation and tumor growth rather than metastasis. However, metastasis is a complex multistep process, in which a cancer cell has to detach from the primary tumor, surviving anoikis, survival in circulation as a single cell or cluster of cells, extravasation from circulation, adaptation to new microenvironment and colonization of the new site of growth. Clinical observations have shown that metastasis is inefficient, as cancer patients take decades to develop overt metastatic disease, despite presence of circulating tumor cells. This suggests that only a few cancer cells are able to survive and establish metastatic tumors. Detailed characterization of specific molecular events that enable survival of the few successful metastatsizers will allow us to target and control metastatic disease.