Metabolism impacts all cellular functions and plays a fundamental role in physiology. Metabolic regulation of hematopoiesis is dynamically regulated under steady-state and stress conditions. It is clear that hematopoietic stem cells (HSCs) impose different energy demands and flexibility during maintenance compared with stressed conditions. However, the cellular and molecular mechanisms underlying metabolic regulation in HSCs remain poorly understood. In this review, we focus on defining the role of fatty acid oxidation (FAO) in HSCs. We first review the existing literature describing FAO in HSCs under steady-state hematopoiesis. Next, we describe the models used to examine HSCs under stress conditions, and, finally, we describe how infection causes a shift toward FAO in HSCs and the impact of using this pathway on emergency hematopoiesis.