Controlled clinically relevant animal models are essential in the ongoing search for increasingly cost-effective methods to reverse clinical death. Acute (up to 12 h) and short-term (up to 24 h) experiments are useful for the study of dying mechanisms and restoration of spontaneous circulation. Although long-term models are difficult and expensive, they are essential to permit lesions to mature, treatments to take effect, secondary deterioration to be recognized, and survival and brain damage to be quantified and compared between treatment groups. The insults studied include temporary complete global head ischemia in monkeys, ventricular fibrillation cardiac arrest in dogs, asphyxial cardiac arrest in rats and dogs, and exsanguination arrest in dogs. Standard external CPR combined with advanced life support is less successful than open-chest CPR or emergency cardiopulmonary bypass after prolonged ventricular fibrillation. Postinsult monitoring of multiple organ systems can be used to explore the postresuscitation syndrome and evaluate novel treatment potentials. Outcome measurements include brain enzyme leakage into the cerebrospinal fluid, neurologic deficit scoring, overall performance categorization, incidence of secondary deterioration, and histopathologic damage scoring of brain and viscera.