Macrophages are innate immune cells that dominate the tumor microenvironment. Environmental cues polarize tumor-associated macrophages (TAMs) into phenotypically and functionally divergent populations that are regarded as anti-tumorigenic (M1) or pro-tumorigenic (M2). It is becoming increasingly evident that the process of polarization incorporates a range of alterations that rather reflects a phenotypic continuum that is mutable. TAMs both manipulate and can be manipulated by tumor cells to ensure tumor progression. In this chapter, we consider the role of TAMS in the tumor microenvironment, and the factors that drive their spatial, phenotypic, and functional changes. Lastly, we consider immunotherapeutic options that would permit targeting macrophage polarity as a strategy to prevent tumor progression.