As important innate immune cells, macrophages are well known for their plasticity and heterogeneity, and their phenotypes are regulated by components of local environment. The origins of macrophages are now thought to be diverse. Some are tissue-colonized macrophages derived from fetal liver and yolk sac, while others are from bone marrow. The proportion of different sources varies from tissues. Tumor-associated macrophages (TAMs) refer to macrophages existing in tumor microenvironment. The phenotypes of TAMs are diverse, so they have different effects in different tumors. They can play an antitumor role and also promote tumor progression by influencing tumor growth, blood vessel formation, metastasis, and immune status. A growing body of evidences gradually reveal the mechanisms that determine the phenotypes and functions of TAMs, which provide a theoretical basis for targeting macrophages as cancer therapy. Significant advances have been made in targeting macrophages by clearing macrophages, inhibiting their recruitment and activation, and repolarizing macrophages to antitumor phenotypes, which have been reported in animal models and clinical trials. Therefore, this chapter discusses the origins, phenotypes of TAMs, and the role of TAMs in cancer immunity. In addition, several macrophage-targeted cancer therapies are also introduced in this chapter.