The fact that opioids constrict the pupil is known to healthcare workers and the lay public. In this chapter, the mechanism of this effect is discussed and how an understanding of this mechanism can be useful to the clinician. There are many parameters that can be measured from the pupil with portable pupillometers. The measure that most closely predicts the onset of severe respiratory depression is pupillary unrest in ambient light (PUAL). This measure is compared to pupil size and pupillary constriction amplitude as a measure of toxic levels of opioids.