It is becoming increasingly clear that interactions between cancer cells, stroma cells and the extracellular matrix (ECM) are pivotal to the processes of neovascularization and tumorigenesis. As tumor stromal components known as tumor associated macrophages (TAMs), mononuclear phagocytes can play a key role in tumor type specific neoangiogenesis by promoting remodeling of the ECM through the production of matrix metalloproteases (MMPs), secreting pro-angiogenic growth factors and stabilizing the tumor vasculature. The growth factor colony-stimulating factor-1 is produced by a wide variety of cancer cells and tumor stroma cells and influences the migration, survival and phenotype of TAMs. Thus, understanding the relationships of the cancer cell with the host environment is key for specifically exploiting tumor growth promoting tumor host interactions for new therapeutic strategies. This review outlines the strategies for targeting CSF-1 in malignancies to influence TAMs in tumor development.