The poorly reactive and dilated pupil observed in a comatose patient is often thought to represent an acute third nerve palsy owing to brain herniation or aneurysm. In the well patient, however, the isolated dilated pupil is unlikely to be owing to a third nerve palsy. It is more commonly owing to other benign causes such as local iris sphincter abnormalities, pharmacologic dilation, tonic pupil syndrome, or sympathetic irritation. This article presents a diagnostic flowchart to help the primary care physician analyze this problem and prevent costly and unnecessary imaging of these patients.