Macrophages are essential elements in the tumor microenvironment, where they can promote tumor growth but also influence the efficacy of anticancer strategies. In conventional therapies, chemotherapy and radiotherapy, TAMs play a dichotomous role, contributing to antitumor activity or hindering the efficacy of cytoreductive therapies. Macrophages express checkpoint ligands and are therefore targets of immunotherapy approaches based on checkpoint inhibitors. Targeted therapies with monoclonal antibodies elicit TAMs to engage in antitumor functions such as antibody-dependent phagocytosis through the activation of Fc receptors. New approaches to exploit macrophage effector functions induced by therapeutic antibodies are under investigation. Finally, strategies aimed at targeting TAM recruitment, survival and functional polarization are advancing towards the clinic. Collectively, TAM-centered strategies will hopefully complement conventional and unconventional anticancer therapies to achieve improved therapeutic benefit.