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Macrophage infiltration has been identified as an independent poor prognostic factor for several cancers. Macrophages also orchestrate various tumor-promoting processes. This observation sparked an interest to therapeutically target these plastic innate immune cells. To date, blockade of colony-stimulating factor 1 (CSF1) or its receptor represents one of the selective approaches to manipulate tumor-associated macrophages. In this review, I discuss the efficacy and safety of various CSF1 receptor tyrosine kinase inhibitors, anti–CSF1 receptor monoclonal antibodies, and anti-CSF1 monoclonal antibodies in clinical development for patients with cancer and highlight potential combination partners, mainly anti–program cell death protein 1 (PD-1) and program cell death protein ligand 1 (PD-L1) antibodies.