Most cancer deaths are due to the development of metastases, hence the most important improvements in morbidity and mortality will result from prevention (or elimination) of such disseminated disease. Some would argue that treatments directed against metastasis are too late because cells have already escaped from the primary tumour. Such an assertion runs contrary to the significant but (for many common adult cancers) fairly modest improvements in survival following the use of adjuvant radiation and chemotherapy designed to eliminate disseminated cells after surgical removal of the primary tumour. Nonetheless, the debate raises important issues concerning the accurate early identification of clonogenic, metastatic cells, the discovery of novel, tractable targets for therapy, and the monitoring of minimal residual disease. We focus on recent findings regarding intrinsic and extrinsic molecular mechanisms controlling metastasis that determine how, when, and where cancers metastasise, and their implications for patient management in the 21st century. © 2007 Elsevier Ltd. All rights reserved.