The tumor microenvironment (TME) plays an important role in cancer growth and progression. Paradoxically, the TME is capable of acting as both a potential barrier and facilitator of tumor proliferation by affecting various processes including local growth resistance, immune system interactions, and the formation of distant metastases. This important interaction between cancer cells and their local environment, composed of immune cells, angiogenic cells, lymphatic endothelial cells and cancer-associated fibroblasts is paramount to determine a cancer cell's ability to grow and ultimately metastasize. It is essential to understand this complex interplay in order to define treatment modalities to target the TME as part of anti-cancer therapy.