<p>The understanding of cancer has evolved from a group of mutated cancerous cells to a complex ecosystem comprising many cellular and non-cellular components. Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment (TME). They actively contribute to cancer outcomes in two ways, either promoting its development and progression or stimulating immune response to combat tumor. Recently, TAMs have been recognized not only as prognostic markers for the outcome of anti-cancer therapy, but also as major players in shaping treatment response. It was also established that therapeutic agents may affect TAMs’ phenotype, and in consequence modulate tumor’s behavior. Therefore, reprogramming of TAMs in order to enhance tumor infiltration and overcome immune suppression is also currently a hot topic in preclinical research. In this review, we discuss the interactions between chemotherapeutic agents and tumor-associated macrophages and their potential consequences for tumor response.</p>