Patients with emphysema may experience reduced health-related quality of life (HRQOL). HRQOL measures have evolved from two different measurement traditions: psychometric theory and decision theory. Psychometric methods typically create a profile of outcomes, whereas decision theory methods offer a summary score on a continuum ranging from 0.0 (for death or worst possible health) to 1.0 (for best possible health). Decision theory methods are better suited for cost-effectiveness studies. Generic HRQOL measures can be applied to any disease population, whereas disease-targeted measures are tailored to a specific clinical condition. Disease-targeted measures are typically more sensitive to clinical change, but cannot offer a comparison basis for different clinical conditions. This article reviews the measurement of HRQOL in patients with emphysema. The National Emphysema Treatment Trial (NETT) offers an example of the application of both generic and disease-targeted, as well as profile and decision theory, methods. The NETT illustrates how HRQOL measures can be used to assess outcomes and estimate cost-effectiveness in a major clinical trial.