Tumorigenesis is not only determined by the intrinsic properties of cancer cells 
but also by their interactions with components of the tumor microenvironment 
(TME). Tumor-associated macrophages (TAMs) are among the most abundant immune 
cells in the TME. During initial stages of tumor development, macrophages can 
either directly promote antitumor responses by killing tumor cells or indirectly 
recruit and activate other immune cells. As genetic changes occur within the 
tumor or T helper 2 (TH 2) cells begin to dominate the TME, TAMs begin to 
exhibit an immunosuppressive protumor phenotype that promotes tumor progression, 
metastasis, and resistance to therapy. Thus, targeting TAMs has emerged as a 
strategy for cancer therapy. To date, TAM targeting strategies have focused on 
macrophage depletion and inhibition of their recruitment into the TME. However, 
these strategies have shown limited therapeutic efficacy, although trials are 
still underway with combination therapies. The fact that macrophages have the 
potential for antitumor activity has moved the TAM targeting field toward the 
development of TAM-reprogramming strategies to support this antitumor immune 
response. Here, we discuss the various roles of TAMs in cancer therapy and their 
immunosuppressive properties, as well as implications for emerging checkpoint 
inhibitor-based immunotherapies. We review state-of-the-art TAM-targeting 
strategies, focusing on current ones at the preclinical and clinical trial 
stages that aim to reprogram TAMs as an oncological therapy.