Immune cell production is governed by a process known as hematopoiesis, where hematopoietic stem cells (HSCs) differentiate through progenitor cells and ultimately to the mature blood and immune cells found in circulation. While HSCs are capable of cell-autonomous regulation, they also rely on extrinsic factors to balance their state of quiescence and activation. These cues can, in part, be derived from the niche in which HSCs are found. Under steady-state conditions, HSCs are found in the bone marrow. This niche is designed to support HSCs but also to respond to external factors, which allows hematopoiesis to be a finely tuned and coordinated process. However, the niche, and its regulation, can become dysregulated to potentiate inflammation during disease. This review will highlight the architecture of the bone marrow and key regulators of hematopoiesis within this niche. Emphasis will be placed on how these mechanisms go awry to exacerbate hematopoietic contributions that drive cardiovascular disease.