Hematopoietic stem cells (HSCs) reside in the bone marrow and are important in replenishing all cells in the blood through a process termed hematopoiesis. One of the defining characteristics of HSCs is that they must be able to balance their self-renewal capacity with their differentiation into committed blood cells in various blood lineages. For these events to occur, HSCs must be tightly regulated in the bone marrow by intrinsic and extrinsic factors to maintain steady hematopoiesis.Recently, the effect on how metabolism regulates HSC function has received a great amount of attention. In particular, lipids have been found to participate in mitochondrial activity to maintain HSCs, a role previously overlooked due to HSCs being thought of as mostly glycolytic. Moreover, there has been a re-emergence of how adipocytes in the bone marrow can regulate HSCs.As these areas evolve, more studies are required to determine the exact contribution of lipids toward HSC maintenance. These studies will allow newer therapeutic targets to help reduce abnormal hematopoiesis such as myelopoiesis, which contributes to many metabolic diseases.