Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet. We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade. Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke. The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied. However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between. Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays.