Variation in spirometric lung function measurements can be ascribed to technical and biological sources and is conveniently classified as within- or between-subject and within- or between-population. A necessary first step is to identify which sources of variation constitute "noise" and which "signal" in the various applications in occupational medicine. This chapter proposes strategies to enhance signal and deal with noise, and it delineates areas in which additional research to strengthen existing information would maximize the usefulness of spirometric measurements.