Physiological measures of exercise performance provide reference points for physical health and fitness. They allow to evaluate the progression of improvements in work capacity with training in the active sportsman or the injured with rehabilitation. Tests are now established in many Sports Clinics to document task-specific exercise performance. Major developments in the area of the molecular health sciences highlight options to reinforce current performance testing with molecular diagnosis. In the following, a personal view of the perspectives of exercise testing at the molecular level is given with respect to endurance performance. The case is developed that local, biopsy-based measures of the transcript response of exercised muscle to endurance work may be used to estimate specificity, pace, and possibly magnitude of adaptation with repeated endurance stimuli. This expression profiling of muscle's adaptive response to an exercise stimulus complements non-invasive, genomic methodologies that have identified the association of exercise performance with modifications in heritable elements (gene polymorphisms). Research applying these tools highlights the possibility that the molecular analysis of sample collected with minimally invasive methodology from peripheral muscle tissue and blood serum can enhance the diagnostic power of current physiological tests, and lend to a future use in predicting the progression and variability of endurance performance with training.