Increasing evidence shows that the interaction between neoplastic cells and the surrounding stroma is a critical factor in solid tumor growth. The tumor stroma is made up of diverse cellular populations including macrophages, lymphocytes, vascular cells, and carcinoma-associated fibroblasts. The complex interactions between the stroma and neoplastic cells are largely unexplored. Initial therapies aimed at disrupting angiogenesis within the tumor microenvironment have met with success in a number of tumor types. An improved understanding of stromal signaling pathways is likely to identify additional novel therapeutic targets.