Clostridium difficile infection is a growing concern in health care and is a worrisome complication in orthopaedics. The incidence and severity of this infection are increasing, although the incidence following orthopaedic surgery is comparatively lower than that seen in patients in most other surgical specialties. The typical geriatric orthopaedic patient may have many risk factors that increase the likelihood of C difficile infection, including advanced age, residence in a long-term care facility, multiple comorbidities, the use of perioperative antibiotics, and a long length of stay. Many antibiotics used for prophylaxis in orthopaedic procedures have been correlated with an increased incidence of C difficile infection. The indications for C difficile testing may vary, and diagnostic methods differ in sensitivity and specificity. The prevention of this infection is multifaceted and consists of practitioner and patient hand hygiene, antibiotic stewardship, contact precautions, and proper environmental cleaning. The main treatment options are metronidazole for mild cases and vancomycin for moderate to severe disease. Up to 40% of cases may have one or more recurrence. Further research is needed to identify novel therapeutic and prevention strategies for C difficile infection.