In the last decade, it has been well-established that tumor-infiltrating myeloid 
cells fuel not only the process of carcinogenesis through cancer-related 
inflammation mechanisms, but also tumor progression, invasion, and metastasis. 
In particular, tumor-associated macrophages (TAMs) are the most abundant 
leucocyte subset in many cancers and play a major role in the creation of a 
protective niche for tumor cells. Their ability to generate an 
immune-suppressive environment is crucial to escape the immune system and to 
allow the tumor to proliferate and metastasize to distant sites. Conventional 
therapies, including chemotherapy and radiotherapy, are often not able to limit 
cancer growth due to the presence of pro-tumoral TAMs; these are also 
responsible for the failure of novel immunotherapies based on immune-checkpoint 
inhibition. Several novel therapeutic strategies have been implemented to 
deplete TAMs; however, more recent approaches aim to use TAMs themselves as 
weapons to fight cancer. Exploiting their functional plasticity, the 
reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral 
macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This 
shift eventually leads to the reconstitution of a reactive immune landscape able 
to destroy the tumor. In this review, we summarize the current knowledge on 
strategies able to reprogram TAMs with single as well as combination therapies.