For decades, biologists have reported a steady decline in the population size of many of the world’s most iconic, large marine and terrestrial mammals. Often, the primary threat to survival is attributed to anthropogenically-driven “habitat destruction” resulting from development, pollution, the degradation of critical resources, altered physical risks and exposure to predators, and climatic events among others. Hidden within these threats is the first line of defense by canids, felids, ursids, cetaceans and pinnipeds, which is to move out of harm’s way. Despite its importance for survival, relatively little is known about the biology of escape in this mammalian group. We find that mounting an escape response requires extraordinary coordination of physiological processes in highly active carnivores. Furthermore, the response is complicated by the habitat in which the animal lives. For terrestrial mammals, escape typically involves species-specific behavioral responses ranging from freezing to flight with the level of speed and maneuvering dictating energetic costs. For example, African leopards (n = 5, Panthera pardus) instrumented with calibrated SMART accelerometer- GPS collars that recorded fine scale (5 min) energetics and movements demonstrated a 38% increase in the cost of locomotion depending on if the animal used a directed high speed gait rather than a slower, cryptic meandering trajectory across the landscape. In a study comparing the chase-escape energetics of instrumented canids (hounds, Canis lupus familiaris) and felids (pumas, Puma concolor) in the Santa Cruz mountains, the behavioral advantage of complex, anaerobic maneuvers by felids was apparent in successful escapes. Combined with a higher cost per stride for the felid (stride cost averaged 5.0 J kg-1 stride-1 for hounds and 7.2 J kg-1 stride-1 for pumas), these evasive maneuvers resulted in a level of energy expenditure that was 3.8 times higher for the animal being chased compared to its pursuer. The physiological costs of escape are even more complex for marine mammals due to the simultaneous, and at times conflicting, responses associated with diving, exercise, and fear. Such conflict is evident in the cardiac patterns of wild narwhals (Monodon monoceros), a deep diving Arctic cetacean. Narwhals wearing an electrocardiographic recorder-stroke monitor showed a paradoxical escape reaction in which an extreme level of diving bradycardia (heart rate = 3-4 beats min-1) was superimposed on a high stroke frequency exercise response. As a result, escape dives required nearly twice the energy of routine dives to similar depths, and rapidly depleted on-board oxygen stores required for supporting aerobic processes. Clearly, acute responses to aversive situations can instigate significant physiological and energetic costs for mammalian carnivores, and will need to be scaled up to predict population effects. Today, as the incidence of unanticipated disturbance by human activities continues to increase on land and in the oceans, the cumulative effects of behavioral modification, reduced time to forage, and such physiological challenges and costs associated with escape responses may well grow into major contributing factors altering the population trajectories of wild mammals.