Macrophages are heterogeneous cells with diverse phenotypes and sometimes opposing functions. These activities are dictated by activating stimuli in their microenvironment. For example, it is well described how CD4+ T helper (Th) cell-derived cytokines result in different macrophage-activation states. However, much less is known on how differentially-activated macrophages, presenting antigen, can drive the major types of CD4+ Th subpopulations, especially in human systems. Many studies have focussed on dendritic cells as the major antigen-presenting cell shaping T cell responses or on murine macrophage-secreted cytokines in the presence of mitogenic-stimuli, such as CD3/CD28, to induce Th polarization. Recent literature is, however, providing evidence that activated antigen-presenting macrophages can be as efficient as dendritic cells in polarising Th cells, especially Th17, and whilst both these cell types co-exist within inflamed tissue, macrophages are more abundant. The bias towards polarization of particular T cell subsets is strongly dependent on the activation state of macrophages. The concept of targeting macrophages to downregulate inflammatory responses may therefore have further reaching consequences by also abrogating pathogenic Th cells in autoimmune or inflammatory diseases.