Neutrophils are becoming recognized as highly versatile and sophisticated cells that display de novo synthetic capacity and potentially prolonged lifespan. Emerging concepts such as neutrophil heterogeneity and plasticity have revealed that, under pathological conditions, neutrophils may differentiate into discrete subsets defined by distinct phenotypic and functional characteristics. Indeed, these newly described neutrophil subsets will undoubtedly add to the already complex interactions between neutrophils and other immune cell types for an effective immune response. The interactions between neutrophils and monocytes/macrophages enable the host to efficiently defend against and eliminate foreign pathogens. However, it is also becoming increasingly clear that these interactions can be detrimental to the host if not tightly regulated. In this review, we will explore the functional cooperation of neutrophil and monocytes/macrophages in homeostasis, during acute inflammation and in various disease settings. We will discuss this in the context of cardiovascular disease in the form of atherosclerosis, an autoimmune disease mainly occurring in the kidneys, as well as the unique intestinal immune response of the gut that does not conform to the norms of the typical immune system.