Contrast-induced encephalopathy (CIE) is a rare encephalopathic condition after the administration of a contrast agent. The diagnosis of CIE is challenging because of the heterogeneity and non-specificity of the clinical presentation. The clinical course is usually favorable with full recovery within 48–72 h in most patients, although comorbidity is of relevance and contributes to the clinical outcome. It is expected that the incidence of CIE is currently increasing, due to an increase in endovascular and diagnostic imaging procedures using iodinated contrast. It is important to include CIE in the differential diagnosis when patients deteriorate during, or immediately after, contrast administration, even when only a small amount of non-ionic contrast agent is used. When CIE is considered to be the most likely explanation for the clinical symptoms, it is advised to refrain from unnecessary additional contrast studies such as angiography or perfusion CT.