Clostridium septicum is a highly virulent, anaerobic, endospore-forming bacterium in the family Clostridiaceae and an important cause of nontraumatic clostridial myonecrosis (gas gangrene) and fatal septicemia in humans and livestock. Unlike C. perfringens, which typically requires predisposing tissue injury, C. septicum is notable for its ability to cause spontaneous gas gangrene arising from bacteremic seeding of intestinal origin, most often in patients with occult colorectal malignancy, hematological malignancies, or neutropenia. The bacterium produces several toxins including alpha-toxin, a pore-forming cytolysin, and hyaluronidase, which facilitate tissue invasion and destruction. Endospores are ubiquitous in soil and the intestinal contents of healthy animals and humans. In livestock, C. septicum causes braxy (sheep abomasitis) and malignant edema, economically significant diseases in sheep and cattle grazing on contaminated pastures. The strong clinical association between spontaneous C. septicum bacteremia and gastrointestinal malignancy means that its isolation from blood cultures warrants urgent investigation for underlying colonic pathology.