A case report of a domesticated ferret (Mustela furo) envenomated by a presumptive rattlesnake (Crotalus sp.) treated successfully and safely with the novel Fab (2′) North American Snake Antivenom (Veteria Labs). The ferret presented with clinical signs of depressed mentation and facial edema following a rattlesnake (Crotalus sp.) bite. It developed hypotension, thrombocytopenia, and ecchymosis following the envenomation. It was treated with Fab (2′) antivenom and given supportive care including crystalloid fluids and analgesia to resolution of clinical signs. This is the first documented case of rattlesnake envenomation in this species. This case supports the efficacy and short-term safety of this Fab (2′) antivenom in this species without the use of antihistamines or glucocorticoids. This report also addresses the current standards of care with thorough review of the literature involving rattlesnake envenomation in zoological species.