The lung function laboratory frequently provides relevant information to the practice of pulmonology. Clinical interpretation of pulmonary function and exercise tests, however, has been complicated more recently by temporal changes in demographic characteristics (higher life expectancy), anthropometric attributes (increased obesity prevalence), and the surge of polypharmacy in a sedentary population with multiple chronic degenerative diseases. In this narrative review, we concisely discuss some key challenges to test interpretation that have been affected by these epidemiologic shifts: (a) the confounding effects of advanced age and severe obesity, (b) the contemporary controversies in the diagnosis of obstruction (including asthma and/or COPD), (c) the importance of considering the diffusing capacity of the lung for carbon monoxide (Dlco)/"accessible" alveolar volume (carbon monoxide transfer coefficient) in association with Dlco to uncover the causes of impaired gas exchange, and (d) the modern role of the pulmonary function laboratory (including cardiopulmonary exercise testing) in the investigation of undetermined dyspnea. Following a Bayesian perspective, we suggest interpretative algorithms that consider the pretest probability of abnormalities as indicated by additional clinical information. We, therefore, adopt a pragmatic approach to help the practicing pulmonologist to apply the information provided by the lung function laboratory to the care of individual patients. Copyright © 2020. Published by Elsevier Inc.