Rattlesnake envenomations are common in some areas of the United States. Although fatal rattlesnake envenomations are rare and usually preventable, morbidity may be significant. Patients may present with localized edema, hypotension, coagulopathy, or thrombocytopenia. Patients with progressive swelling or severe coagulopathy are typically treated with Crotalidae polyvalent antivenin. We present a series of 4 patients with unusual complications of rattlesnake envenomation to illustrate the wide spectrum of disease that may be encountered. These case presentations include anaphylaxis to rattlesnake venom, an acute airway emergency, progressive and marked edema with a large pleural fluid collection, and death.