As the obesity epidemic has worsened, its impact on lung health and disease has become progressively evident. The interactions between obesity and the accompanying metabolic syndrome and diseases such as asthma, pneumonia, and acute respiratory distress syndrome (ARDS) have proven complex and often counterintuitive in human studies. Hence, there is a growing need for relevant experimental approaches to understand the interactions between obesity and the lung. To this end, researchers have increasingly exploited mouse models combining both obesity and lung diseases, including ARDS, pneumonia, and asthma. Such models have both complemented and advanced the understanding we have gained from clinical studies and have allowed elegant dissections of obesity’s effects on the pathogenesis of lung disease. Yet these models come with several critically important caveats that we must reflect on when interpreting their results.