Cardiometabolic and vascular disease, with their associated secondary complications, are the leading cause of morbidity and mortality in Western society. Chronic inflammation is a common theme that underlies initiation and progression of cardiovascular disease. In this regard, monocytes/macrophages are key players in the development of a chronic inflammatory state. Over the past decade, epigenetic modifications, such as DNA methylation and posttranslational histone processing, have emerged as important regulators of immune cell phenotypes. Accumulating studies reveal the importance of epigenetic enzymes in the dynamic regulation of key signaling pathways that alter monocyte/macrophage phenotypes in response to environmental stimuli. In this review, we highlight the current paradigms of monocyte/macrophage polarization and the emerging role of epigenetic modification in the regulation of monocyte/macrophage phenotype in obesity, diabetes mellitus, atherosclerosis, and abdominal aortic aneurysms.