Exercise tests are commonly used in clinical practice for both functional and diagnostic assessments. Many exercise tests are designed to produce a single measurement relevant to a specific clinical setting such as a timed walking distance as a measure of functional capacity in rehabilitation candidates or the presence of ECG changes consistent with myocardial ischemia in patients with chest pain. Cardiopulmonary exercise testing (CPX) measures a broader range of variables related to cardiorespiratory function, including expiratory ventilation (VE) and pulmonary gas exchange (oxygen uptake [VO2] and carbon dioxide output [VCO2]), along with the ECG and blood pressure, with the goal of quantitatively linking metabolic, cardiovascular, and pulmonary responses to exercise. 1–3 With increased availability of instruments for the facile measurement of exercise gas exchange, experience with CPX has expanded from clinical research applications to a broad range of clinical practice settings. 4 Interpretation of CPX for clinical purposes includes comparison of data from individual patients with those from healthy and disease populations. Substantial data are available characterizing exercise responses of patients with certain common heart and lung diseases, providing a basis for using CPX to compare individual patients’ impairment relative to others from the same populations. Diagnostic applications of CPX, eg, for evaluating unexplained dyspnea or exercise intolerance, also rely on a comparison of patients’ data with those of patients with known diagnoses. In clinical practice, in contrast to much of the research related to specific disorders, patients frequently have multiple medical problems, confounding the assessment of impairment or the attribution of symptoms to one or another condition. Although there are few systematic analyses of the effects of coexistent conditions on exercise responses, an advantage of CPX compared with other forms of testing is the potential for gaining insight into these interactions. This review highlights CPX findings in selected clinical populations and the implication of these observations to the clinical evaluation of patients with heart and/or lung diseases.