Unfortunately, fires are common events both in urban and rural portions of the United States. Smoke inhalation is the leading fire-related cause of death. The elemental combustion products of fire are light, heat, and smoke. Smoke is a very complex mixture of potentially harmful substances. Although a relatively rare presenting event to small animal hospitals, when animal fire victims do appear, clinicians must know how to recognize the signs of smoke inhalation and how to successfully deal with them. This discussion will investigate the toxic nature of fire smoke, its mechanism of action upon respiratory tissues, the clinical signs displayed, and its diagnosis and treatment. Differential diagnoses of smoke inhalation and prevention and prognosis will also be explored. Veterinary hospitals should have set protocols in place for managing animal victims of smoke inhalation in order to ensure a successful outcome.