Granulomatous immune responses are interesting models for the effector phase of immunity, in that granulomas can be part of both immune protection and disease pathology during the course of various infectious and autoimmune diseases. Focusing mainly on granulomas induced by Schistosoma or Mycobacterium infection, this article reviews T-cell recruitment, local cytokine networks and the regulation of cytokine networks by neuropeptides in granulomas. In addition, different activation pathways for macrophages residing in granulomas are discussed. Granulomas are unique inflammatory sites that offer a challenging and rewarding model to study immunity.