Chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), are a major health issue worldwide due to their growing prevalence and high economic costs, which include prolonged medication use and frequent hospitalizations. Both asthma and COPD are incurable, and each is characterized by chronic inflammation, tissue remodeling, and ultrastructural alterations that might not be amenable to available therapies. Mesenchymal stromal cells (MSCs) are non-hematopoietic, immunosuppressive cells found in bone marrow, adipose tissue, placenta, and other tissues and have demonstrated anti-inflammatory actions in a number of preclinical models of asthma and COPD. Although the entire repertoire of action of MSCs has not been elucidated, there is growing interest in the potential clinical utility of MSC-based cell therapy in chronic respiratory diseases. The present review will focus on the most recent mechanisms that have been elucidated from preclinical studies in asthma and COPD. In addition, a comprehensive review of clinical trials conducted to date will be presented.