The most dangerous attribute of cancer cells is their ability to metastasize. Throughout the process of metastasis, tumor cells interact with other tumor cells, host cells and extracellular molecules. This brief review explores how a new class of molecules - metastasis suppressors - regulate tumor cell-microenvironmental interactions. Data are presented which demonstrate that metastasis suppressors act at multiple steps of the metastatic cascade. A brief discussion for how metastasis suppressor regulation of cellular interactions might be exploited is presented. © 2008 Springer Science+Business Media B.V.