A 68-year old male with stage IV NSCLC presented with speech difficulties after receiving 3 monthly cycles of carboplatin, pemetrexed and pembrolizumab. On exam, he had moderate dysarthria, reduced fine finger dexterity and right pronator drift. MRI brain with contrast showed multifocal areas of T2 hyperintensity involving supratentorial white matter, pons, middle cerebellar peduncles, and cerebellar hemispheres. CSF studies, including cytology were negative. HSV, VZV, EBV, CMV, JC virus PCR in CSF were negative. Serum HIV was negative and paraneoplastic panel was unrevealing. A presumptive diagnosis of ICI- associated encephalitis was made. Pemetrexed, the other chemotherapy agent used here, has been associated with posterior reversible encephalopathy syndrome; the clinical picture was inconsistent with this diagnosis.  He was started on dexamethasone 4 mg twice daily, increased to 6 mg twice daily after 2 weeks. He also received 0.4g/kg/day IVIG treatment for 5 days followed by IV methylprednisolone for 5 days. Given the lack of improvement in his neurological status despite treatment, and his advanced cancer, the patient decided to not pursue further treatment. He was discharged to hospice.