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Helminths have evolved numerous pathways to prevent their expulsion or elimination from the host to ensure long-term survival. During infection, they target numerous host cells, including macrophages, to induce an alternatively activated phenotype, which aids elimination of infection, tissue repair, and wound healing. Multiple animal-based studies have demonstrated a significant reduction or complete reversal of disease by helminth infection, treatment with helminth products, or helminth-modulated macrophages in models of allergy, autoimmunity, and sepsis. Experimental studies of macrophage and helminth therapies are being translated into clinical benefits for patients undergoing transplantation and those with multiple sclerosis. Thus, helminths or helminth-modulated macrophages present great possibilities as therapeutic applications for inflammatory diseases in humans. Macrophage-based helminth therapies and the underlying mechanisms of their therapeutic or curative effects represent an under-researched area with the potential to open new avenues of treatment. This review explores the application of helminth-modulated macrophages as a new therapy for inflammatory diseases.