Rabies is the most important viral zoonosis from a global perspective. Modern human postexposure prophylaxis consists of potent vaccines and local infiltration of rabies immune globulins (RIGs), but the latter biologicals are not widely available or affordable. Monoclonal antibodies (Mabs) offer several theoretical advantages over RIGs. To this end, several human and equine RIGS, alone or in combination with vaccine, were investigated for postexposure efficacy in a Syrian hamster model, compared with a single neutralizing murine Mab. Preliminary results suggest that: (1) animal models continue to provide utility as human surrogates in the demonstration of product efficacy against rabies; (2) RIG preparations differ substantially in experimental effectiveness and clearance; and (3) relevant alternatives, such as Mabs, should be pursued for future improvements to human rabies prevention.