Tumors are populated with different cells of the immune system, each of which has the potential for pro‐ or antitumor functions. Macrophages are the numerically dominant type of myeloid cell in cancer and are suspected of having predominantly protumor functions. Key questions in cancer research concern the relationships between macrophages and anatomically different kinds of cancers, what specific properties of macrophages are involved in protumor functions and whether either macrophage numbers or functions can be modulated to enhance existing cancer therapies, for example, by reducing the immunosuppressive milieu such that anti‐tumor T cells can provoke antitumor immunity. Accordingly, several antimacrophage preclinical modalities have been attempted and revealed substantial clinical barriers to their use. Therefore, understanding and targeting the specific pathways associated with protumor functions of macrophages, rather than macrophages themselves is a promising approach for both basic research and therapeutic development.