The tumor microenvironment (TME) consists of cells, soluble factors, signaling molecules, extracellular matrix, and mechanical cues that can promote neoplastic transformation, support tumor growth and invasion, protect the tumor from host immunity, foster therapeutic resistance, and provide niches for dormant metastases to thrive. An American Association for Cancer Research (AACR) special conference held on November 3-6, 2011, addressed five emerging concepts in our understanding of the TME: its dynamic evolution, how it is educated by tumor cells, pathways of communication between stromal and tumor cells, immunomodulatory roles of the lymphatic system, and contribution of the intestinal microbiota. These discussions raised critical questions on how to include the analysis of the TME in personalized cancer diagnosis and treatment. Cancer Res; 72(10); 2473-80. (C) 2012 AACR.