High-intensity intermittent exercise (HIIE) has been applied in competitive sports for more than 100 years. In the last decades, interval studies revealed a multitude of beneficial effects in various subjects despite a large variety of exercise prescriptions. Therefore, one could assume that an accurate prescription of HIIE is not relevant. However, the manipulation of HIIE variables (peak workload and peak-workload duration, mean workload, intensity and duration of recovery, number of intervals) directly affects the acute physiological responses during exercise leading to specific medium- and long-term training adaptations. The diversity of intermittent-exercise regimens applied in different studies may suggest that the acute physiological mechanisms during HIIE forced by particular exercise prescriptions are not clear in detail or not taken into consideration. A standardized and consistent approach to the prescription and classification of HIIE is still missing. An optimal and individual setting of the HIIE variables requires the consideration of the physiological responses elicited by the HIIE regimen. In this regard, particularly the intensities and durations of the peak-workload phases are highly relevant since these variables are primarily responsible for the metabolic processes during HIIE in the working muscle (eg, lactate metabolism). In addition, the way of prescribing exercise intensity also markedly influences acute metabolic and cardiorespiratory responses. Turn-point or threshold models are suggested to be more appropriate and accurate to prescribe HIIE intensity than using percentages of maximal heart rate or maximal oxygen uptake.