Ustekinumab is a fully human immunoglobulin that binds to important cytokines in the pathogenesis of psoriasis. In this case report, Gratton et al describe a single case of reversible posterior leukoencephalopathy syndrome (RPLS) observed in a ustekinumab clinical trial for psoriasis. A reversible neurologic syndrome, RPLS is characterized by acute headache, visual disturbances, altered mental status, seizures, transient cerebral edema, and infarction in the posterior brain. The syndrome is often associated with hypertension, autoimmune diseases, and treatment with immunosuppressive agents. The clinical features of this case were atypical of drug-associated RPLS. Although the relationship between ustekinumab and RPLS remains unclear, this case emphasizes the need for dermatologists to recognize the syndrome and refer patients for appropriate evaluation and treatment.