Macrophages not only initiate and modulate immune responses, but also are the final effector cells. Recent studies suggested that macrophages conventionally associated with IFN-gamma dominant Th1-type responses and also playing an essential role in the Th2-type inflammatory response, exhibit a quite different activation from the classically activated macrophages (CAM Phi) stimulated during Th1-type responses, therefore named as alternatively activated macrophages (AAM Phi). AAM Phi have multiple effects during helminth infection, including control of inflammatory reaction, contribution to fibrosis and repair at the site of injury, and anti-helminth effect. This article reviews recent findings regarding the role of AAM Phi in the development of disease and host protection following helminth infection.