Display omitted •Macrophages are frequently reported in the microenvironment of head and neck cancers.•Macrophages may harbor two phenotypes: antitumoral M1 or protumoral M2.•Macrophages in head and neck cancers have been associated with a poor prognosis.•Different strategies are developed toward macrophages as a therapeutic target.•Macrophages modulators are investigated alone or in combination with standard Therapies. The microenvironment of solid tumors has become a promising target for future therapies modulating immune cells. Patients with advanced head and neck cancer, which still portends a poor outcome, are particularly in need of innovative approaches. In oral squamous cell carcinoma, high density of tumor-associated macrophages (TAMs) appears consistently associated with poor prognosis, whereas data are currently limited for other head and neck sites. Several approaches to block TAMs have been investigated, including TAMs inactivation by means of the colony stimulating factor 1 (CSF-1)/CSF-1 receptor (CSF-1R) inhibitors or strategies to reprogram TAMs from M2 protumoral phenotype toward M1 antitumoral phenotype. This review focuses on both prognostic and therapeutic aspects related to TAMs in head and neck carcinomas.