A 40-year-old Caucasian lady with focal crescentic glomerulonephritis (p-ANCA) demonstrated by kidney biopsy, was treated with intravenous pulse steroids followed by weekly outpatient rituximab infusions (375 mg/m2). Five days after the fourth and final rituximab infusion, she developed headaches, altered mental status and seizures. Upon transfer to our facility, magnetic resonance imaging of the brain revealed cortical white matter changes suggestive of possible progressive multifocal leukoencephalopathy (PML) or posterior reversible encephalopathy syndrome (PRES). She was aggressively treated with antihypertensives, anti-seizure medications, intravenous steroids, plasmapheresis and ventilatory support while awaiting cerebrospinal fluid analysis and polymerase chain reaction on John Cunningham virus DNA. She had a complete recovery and, at 1 year follow up, was found to be doing well. Awareness of potential complications of rituximab therapy, such as PRES or PML is critical in providing appropriate treatment.