Phenotype is defined as the outward physical manifestation of patients with chronic obstructive pulmonary disease (COPD); anything that is part of their observable structure, function, or behavior. As such, for patients with COPD, the time has come to move from a disease expressed solely by the degree of airflow limitation, to a much broader and resourceful characterization of COPD. Recent advances in the detection of specific clinical phenotypes, such as persistent hypoxemia, hyperinflation with inhomogeneous emphysema, frequent exacerbators, and patients with peripheral muscle dysfunction, are resulting in specific forms of approaches to include therapy that are affecting outcomes. Further, the investigation of the differential influence of gender on the development of COPD is finally catching our attention. In the area of basic science, we are beginning to understand different expressions of disease through genomics, proteomics, and metabonomics. Extensions of these findings and that of neglected aspects that may explain the clinical course of certain patients, such as their psychologic background, will certainly increase our understanding and provide more solid scientific rationale to the phenotypic characterization of patients with COPD. Further, such understanding will not only help explain the manifestations and course of the disease in particular patients but also help select for specific therapies. The hope is that, coupled with primary and secondary prevention, we can reverse the current epidemic and we can improve the well-being of patients affected by COPD.