Pylephlebitis usually occurs secondary to infection in the region drained by the portal venous system. We describe a case of pylephlebitis at our institution and examine 18 other cases culled from the literature since 1979, reviewing diagnostic and management issues. A precipitating focus of infection (most commonly diverticulitis) was identified in 13 (68%) of the cases. Bacteremia (often polymicrobial) was present in 88% of the patients. The most common blood isolate was Bacteroides fragilis. Overall mortality was 32%, but most of the patients who died had severe sepsis prior to the initiation of antibiotic therapy. In no case was improvement in a patient's clinical status clearly attributable to the use of heparin, but some beneficial effect of anticoagulation could not be ruled out. This report is the first to examine the published experience with pylephlebitis during the era of antibiotics and modern imaging and is also the first to review critically the role of anticoagulation in the management of this disease.