Chronic obstructive pulmonary disease (COPD) is a complex inflammatory disease with a myriad of pulmonary and nonpulmonary disease manifestations. COPD is a heterogeneous disease consisting of emphysematous destruction, airway inflammation, remodeling, and obstruction. Once conceptualized as a unidimensional disease isolated to the lung, it is now recognized to have significant systemic manifestations, such as osteoporosis, cardiovascular disease, and skeletal muscle wasting. As the clinical phenotypic expressions of COPD become more precisely characterized, so does the pathogenesis of this disease. Great strides are now being made in our understanding of genetic susceptibility, airway inflammation, the immune response to cigarette smoke, and inflammatory biomarkers. This review will discuss the most recent progress on selected topics in COPD pathogenesis, inflammation, and genetics. With time, we hope to expand our current understanding to predict who will develop disease and who will not, and why some patients develop particular disease phenotypes. In addition, we hope to clarify the inflammatory mechanisms involved in order to develop novel therapies and identify disease biomarkers that will lead to better tools for monitoring disease activity. Finally, we hope to develop treatments aimed at lung regeneration and repair, to reverse lung damage that has already occurred. We are optimistic that novel therapies like gene therapy and advanced antiinflammatory agents will be in our future. Judging by the progress made in the last decade, these tools may soon become a reality.