Macrophages are important, multifunctional cells in the innate immune system. Their ability adopt a spectrum of phenotypes that perform greatly different functions in response to diverse activators has become increasingly recognized (1). IFN-γ is an important pro-inflammatory cytokine in responses to certain pathogens, promoting toll-like receptor expression and inducing greater production of nitric oxide, pro-inflammatory cytokines, such as TNFα (2, 3) and extracellular proteases, including some metalloproteinases (4), which together promote invasion of macrophages to sites of inflammation and enhance microbial killing. IFN-γ is also an established link between the innate and acquired immune systems, especially in the context of autoimmunity, where it not only promotes activation of Thelper1 lymphocytes but also increases major histocompatibility complex (MHCII) expression leading to enhanced antigen presentation by macrophages (3). Macrophages activated by IFN-γ are believed to provoke tissue injury, for example joint destruction during rheumatoid arthritis and atherosclerotic plaque rupture leading to myocardial infarctions (5). On the other hand, IL-4 or IL-13 provoke a macrophage phenotype that has greater scavenger receptor activity and increased release of anti-inflammatory and fibrogenic factors (6, 7), suggesting a primary role in clearance of cell debris and promotion of tissue repair. Although apparently more benign, these macrophages may help tumor cells evade immune surveillance and can provoke allergy or lung hypersensitivity (6, 7). Greater understanding of the mechanisms that underlie generation of these diverse macrophage phenotypes is, therefore, warranted in order to design strategies to avoid these unwanted complications.