Cancers are not just masses of malignant cells but complex ‘rogue’organs, to which many other cells are recruited and can be corrupted by the transformed cells. Interactions between malignant and non-transformed cells create the tumor microenvironment (TME). The non-malignant cells of the TME have a dynamic and often tumor-promoting function at all stages of carcinogenesis (Hanahan and Coussens, 2012). Intercellular communication is driven by a complex and dynamic network of cytokines, chemokines, growth factors, and inflammatory and matrix remodeling enzymes against a background of major perturbations to the physical and chemical properties of the tissue. The evolution, structure and activities of the cells in the TME have many parallels with the processes of wound healing and inflammation, but cells such as macrophages are also found in cancers that have no known association with chronic inflammatory conditions (Grivennikov et al., 2010; Hanahan and Weinberg, 2011; Mantovani et al., 2008). One reason for this is that inflammatory and wound-healing processes are activated downstream of oncogenic mutations in the malignant cells (Mantovani et al., 2008). This Cell Science at a Glance article will describe the functions of major non-malignant cell types that are found in the TME of most human and experimental cancers; the cells of the immune system, the tumor vasculature and lymphatics, as well as fibroblasts, pericytes and adipocytes, and will discuss their importance in cancer development, spread and response to treatment (see poster). The common features of many TMEs suggest that targeting the nonmalignant cells, or mediators of their communication, have applications across different tumor types and could also complement other treatment options.