Although smoking results in lung pathology in many, still not all smokers develop chronic obstructive pulmonary disease (COPD). Roughly a quarter of patients with COPD have never smoked. An understanding of both host and environmental factors beyond smoking that contribute to disease development remain critical to understanding disease prevention and ultimately effectively intervene. In this article, we summarize host factors, including genetics and gender, as well as early-life events that contribute to the development of COPD.