Cardiopulmonary exercise testing (CPET) is an established method for evaluating dyspnea and ventilatory abnormalities. Ventilatory reserve is typically assessed as the ratio of peak exercise ventilation to maximal voluntary ventilation. Unfortunately, this crude assessment provides limited data on the factors that limit the normal ventilatory response to exercise. Additional measurements can provide a more comprehensive evaluation of respiratory mechanical constraints during CPET (e.g., expiratory flow limitation and operating lung volumes). These measurements are directly dependent on an accurate assessment of inspiratory capacity (IC) throughout rest and exercise. Despite the valuable insight that the IC provides, there are no established recommendations on how to perform the maneuver during exercise and how to analyze and interpret the data. Accordingly, the purpose of this manuscript is to comprehensively examine a number of methodological issues related to the measurement, analysis, and interpretation of the IC. We will also briefly discuss IC responses to exercise in health and disease and will consider how various therapeutic interventions influence the IC, particularly in patients with chronic obstructive pulmonary disease. Our main conclusion is that IC measurements are both reproducible and responsive to therapy and provide important information on the mechanisms of dyspnea and exercise limitation during CPET.