No tumor is an island. Chemical and physical forces exerted by the diverse cellular populations that surround a tumor - its so-called microenvironment - shape development and progression. Manipulating these 'ecological' factors is increasingly attractive therapeutically, as Mina Bissell and colleagues discuss in the following pages. And just as the cellular neighborhood is diverse, tumors enriched in these environments comprise a variety of cell types. In this heterogeneous mix, increasing evidence points to so-called cancer stem cells as the root of malignancy. Irving Weissman and Michael Clarke discuss the implications for leukemias on page 35, and on page 37 Peter B. Dirks discusses cancer stem cells in the brain.