Endurance athletes demonstrate an exceptional resistance to fatigue when exercising at high intensity. Much research has been devoted to the contribution of aerobic capacity for the economy of endurance performance. Important aspects of the fine-tuning of metabolic processes and power output in the endurance athlete have been overlooked. This review addresses how training paradigms exploit bioenergetic pathways in recruited muscle groups to promote the endurance phenotype. A special focus is laid on the genome-mediated mechanisms that underlie the conditioning of fatigue resistance and aerobic performance by training macrocycles and complements. The available data on work-induced muscle plasticity implies that different biologic strategies are exploited in athletic and untrained populations to boost endurance capacity. Olympic champions are probably endowed with a unique constitution that renders the conditioning of endurance capacity for competition particularly efficient.