An 85-year-old male nursing home resident presented with confusion and lethargy of 2 days' duration. His medical history was remarkable for chronic renal insufficiency; prostate cancer, for which irradiation had been given; rectosigmoid resection with Hartman pouch secondary to bowel obstruction; and multiple episodes of Clostridium difficile colitis in the past few months. On examination, the patient had a temperature of 38ΥC, heart rate of 107 beats/min, respirations of 19/min, blood pressure of 105/51 mm Hg, and oxygen saturation of 96% while breathing room air. Tenderness was noted in the right lower quadrant of the abdomen, but the ostomy site was healed. Laboratory studies yielded a white blood cell count of 40.1 × 109/L, and the anion gap was 17 mEq/L. Intravenous antibiotic therapy was administered. A stool sample was positive for C difficile toxin. On day 2 of hospitalization, yellow pseudomembranes were visible on the patient's ostomy stump. His white blood cell count increased to 74.5 × 109/L, and his mental status was deteriorating. The treatment options were discussed with the patient's son, who decided on palliative care. Pseudomembranous colitis is an acute inflammatory disease of the colon associated with C difficile. It is most commonly caused by antibiotic therapy, which alters normal bacterial flora. Pseudomembranous colitis usually presents as profuse watery or mucoid foul-smelling stool with abdominal cramping and fever. The differential diagnoses are inflammatory bowel disease; ischemic colitis; malabsorption; bacterial colitis caused by Salmonella species, Campylobacter species, or Escherichia coli; and other causes of watery diarrhea such as Norwalk virus and Giardia. The diagnosis is most commonly made by stool assay for Clostridium toxin (95% sensitive) and other laboratory abnormalities, including elevated white blood cell count, fecal leukocytosis, decreased albumin level, and electrolyte imbalance. The drug of choice for pseudomembranous colitis is metronidazole; for repeated infection, vancomycin is the preferred treatment. Anti-diarrheal agents should be avoided if C difficile colitis is suspected.