This chapter summarizes as a primer, individual physiological traits that contribute to overall endurance, endurance-related traits, and performance during endurance events. It also summarizes basic molecular pathways that modify traits associated with endurance phenotypes and informs subsequent chapters on the genetic influences of these traits. Healthy humans have a remarkable capacity to engage in endurance activities. Genetic understanding of endurance capacity describes an emergent group of well-conserved traits which span an organizational hierarchy from subcellular to organismal. The endurance phenotype is characterized by metabolic flexibility. This point is ultimately underscored by natural selection of “thrifty�? genes directed to promote energy storage and spare carbohydrate use. Given the importance of duration to endurance-type exercise, metabolic flexibility is perhaps best characterized by the ability to the support ATP regeneration via multiple macronutrient substrates in order to maintain steady-state workload demands. Endurance exercise evokes prominent alterations to the integrated cardiorespiratory response.