Macrophages are key regulatory cells of the immune system involved in initiating and directing the innate and specific immune responses, the systemic acute phase response, tissue repair, and tissue remodeling. In the early stages of a challenge from invading microorganisms or from tissue injury, macrophages defend local and systemic homeostasis by initiating a complex series of cellular, biochemical, and behavioral events. These pathophysiological adjustments are mediated by an extensive variety of communication molecules, including: cytokines, cytokine inhibitors, endocrine hormones, eicosanoids, neurotransmitters, and reactive oxygen intermediates. The cytokines produced by macrophages (monokines) are not well characterized relative to their mammalian counterparts, but a variety of chemokine, pro-inflammatory, and colony-stimulating factor activities have been described. Although the sequence homology, and thus species cross-reactivity, between avian and mammalian cytokines is typically low, the functional characteristics appear to be generally similar. The pro-inflammatory cytokines are important initiators and regulators of the local immune response. They are also released in sufficient quantities during some infections to coordinate a systemic acute phase response that impacts the growth, reproduction, and well-being of poultry. An understanding of the mechanisms and molecules used by macrophages to regulate immune and inflammatory responses may permit the development of products, diets, or husbandry techniques to modulate immunity for the enhancement of the productivity of poultry.