Macrophages make up a crucial aspect of the immune system, carrying out a variety of functions ranging from clearing cellular debris to their well-recognized roles as innate immune cells. These cells exist along a spectrum of phenotypes but can be generally divided into proinflammatory (M1) and anti-inflammatory (M2) groups, representing different states of polarization. Due to their diverse functions, macrophages are implicated in a variety of diseases such as atherosclerosis, lupus nephritis, or infection with HIV. Throughout their lifetime, macrophages can be influenced by a wide variety of signals that influence their polarization states, which can affect their function and influence their effects on disease progression. This review seeks to provide a summary of how GM-CSF and M-CSF influence macrophage activity during disease, and provide examples of in vitro research that indicate competition between the two cytokines in governing macrophage polarization. Gaining a greater understanding of the relationship between GM-CSF and M-CSF, along with how these cytokines fit into the larger context of diseases, will inform their use as treatments or targets for treatment in various diseases.