Northern environments present ecological and physiological problems for homeotherms that require adaptations to cope with severe and less predictable physical factors while at the same time continuing to have to cope with the biological ones, such as competition and predation. The stress axis plays a central role in these adaptations and I discuss the range of solutions that birds and mammals have evolved. The stress response in these animals is not static when a challenge occurs, but may be modulated depending on the biological function during the annual cycle (breeding versus nonbreeding), either under-responding to permit reproduction (some song birds) or responding vigorously, yet not having this compromise reproduction (Arctic ground squirrels). Both may trade off survival for reproduction. In contrast, the snowshoe hare shows the expected stress response to chronic high predation risk over 2–3 years: body resources are geared to survival and reproduction is inhibited. Two long term, persistent, and pervasive changes will confront northern birds and mammals in the 21^st century: global change and persistent organochlorine pollutants (POPs). These may result in either adaptations or shifts in distribution and abundance. For the former, latitudinal variation in the stress axis may help song birds respond rapidly; population variation in the stress axis response is unknown in northern mammals and relatively sedentary mammals may be unable to shift their distribution rapidly to adjust major climate shifts. For the latter, the few POPs studies that have examined the stress axis indicate marked negative effects.