Macrophages are potent hematopoietic cells which can activate or suppress immune functions. They show plasticity influenced by surrounding environmental milieu. Tumor cells protect themselves by developing immunosuppressive tumor microenvironment (TME), which is composed of tumor cells, infiltrating cells, and stromal cells. Macrophages are the major infiltrating cells in TME with mainly M2 phenotype, playing major roles in skewing TME into suppressive immune state with decreased anti-tumor immunity. The objectives of this chapter are to provide the mini-review on macrophage subtypes and the roles in cancer immunology and to present recent advancement in investigations on therapeutic approaches related to macrophages in malignant tumors, with special focus on cutaneous malignancies. Tremendous efforts have been performed and various measures have been developed to concur immunosuppressive TME to restore anti-tumor immunity by immune checkpoint inhibitors, cancer vaccines, CAR-T cells, oncolytic viruses, and reprogramming of tumor-associated macrophages (TAMs), which were concisely reviewed. Literature survey with the following keywords—melanoma, macrophages, and reprogramming—retrieved 55 literatures, and the relevant literatures were roughly summarized. Many investigations revealed the potential efficacy of various therapeutic measures, but success in animal experiments does not always mean therapeutic success in humans. Several novel therapeutics have been developed or are in clinical trials with therapeutic efficacy, but some of them showed unignorable side effects. Efficient drug delivery system would decrease undesired side effects and enhance the therapeutic efficacy of these novel therapeutic measures. The combination of the novel therapy with conventional chemotherapy or with other immune-stimulating modalities would show synergistic efficacy which should be carefully prepared and monitored when applied in humans.