A 22-year-old woman was admitted to the hospital with pneumonia, urinary tract infection, anemia, thrombocytopenia, and leukocytosis. After receiving moxifloxacin for 5 days, she experienced diarrhea with cramping and abdominal pain. She was diagnosed with Clostridium difficile-associated diarrhea (CDAD) after C. difficile toxin was identified in a stool specimen. Metronidazole was begun, and the CDAD resolved with continued moxifloxacin administration. Virtually any antibiotic can lead to development of CDAD through disruption of the normal colonic flora, allowing for overgrowth of C. difficile. Although moxifloxacin is generally well tolerated, clinicians should be aware of its potential for inducing CDAD.