Exercise intolerance occurs when a person cannot sustain a required work rate sufficiently long for the successful completion of the task. The ability to sustain an exercise task depends largely on the ability to transport oxygen to its utilization site as the terminal oxidant of the mitochondrial electron transport chain in skeletal muscle, and to clear the resulting metabolically produced carbon dioxide and lactic acid. This process requires the kinetics of the associated ventilatory, pulmonary gas exchange, and cardiovascular system responses to be closely coordinated with the intramuscular requirements for ATP utilization and resynthesis. As the kinetic features of these system responses are highly intensity dependent, any meaningful interpretational frame of reference has to provide a rigorous definition of exercise intensity that takes into account individual differences in the threshold for blood lactate increase relative to maximal aerobic capacity. This article provides an introduction to the fundamentals of normal operation of these systems and their integrated patterns of response to particular stress profiles.