Within most human and murine cancers there is an abundant macrophage population, attracted to the tumor microenvironment by cytokines and chemokines such as CSF-1 (M-CSF) and CCL2 (MCP-1) (Cell 124:263–266, 2006). Despite their intrinsic antitumor activity there is usually, but not always, a positive association between the extent of the macrophage infiltrate in tumors and a bad prognosis (Cell 124:263–266, 2006; Nat Rev Cancer 4:71–78, 2004). According to Condeelis and Pollard (Nat Rev Cancer 4:71–78, 2004), tumor-associated macrophages are obligate partners for malignant cell migration, invasion, and metastasis. These conclusions are based not only on association studies, but also on experiments demonstrating that ablation of macrophage function, or their infiltration into experimental tumors, inhibits growth and metastasis (J Exp Med 193:727–740, 2001). While it has become well appreciated that the extensive macrophage infiltrate of tumors can correlate with tumor progression, there is little understanding of the precise nature of interactions between malignant cells and macro-phages and the mechanisms by which these promote cancer. There are several experimental approaches to study the interactions between macrophages and tumor cells in vitro, which we will describe here.