Two cases of serious infection following catfish spine-related injuries are presented, and the literature on this topic is reviewed. The organisms usually involved in such infections are Vibrio species, Aeromonas hydrophila, Enterobacteriaceae, Pseudomonas species, and components of the flora of the human skin. Irrigation, exploration, and culture of these wounds as well as immunization of the patient against tetanus are recommended. Patients with hepatic disease or chronic illness and immunocompromised individuals are at unusually high risk of fulminant infection due to Vibrio and Aeromonas species and should be treated with antibiotics after sustaining a water-associated wound. Patients with normal host defense mechanisms but with late wound care, punctures involving a bone or a joint, progressive inflammation hours after envenomation, fever, or signs of sepsis are at high risk for secondary infection and should receive definitive wound care and antibiotics. For moderate to severe infections, one of the following combinations constitutes a reasonable empirical regimen: (1) a tetracycline and a broad-spectrum, beta-lactamase-stable beta-lactam antibiotic, or (2) a tetracycline, a beta-lactamase-stable penicillin, and an aminoglycoside.