Conservation strategies for imperiled species are frequently based on identifying and addressing the probable causes of population decline, an approach known as the declining population paradigm. Causes, however, are frequently linked to demographic outcomes by multiple mechanisms, and failing to target the primary mechanisms can reduce the effectiveness and efficiency of conservation actions. Increasingly, conservation strategies also need to consider emerging threats, such as climate change. Here, we use boreal caribou (Rangifer tarandus caribou), a threatened ecotype of woodland caribou, as a case study to illustrate how landscape disturbance and climate change can each exert negative demographic effects on caribou through multiple and complex mechanisms. We reviewed the extensive literature focused on woodland caribou to identify and assess the relative importance of each putative mechanism. While disturbance-mediated apparent competition, the expansion of novel predators, and altered predator behavior appear to be primary mechanisms dictating past and current declines of caribou, climate change has increasing potential to exert strong direct and indirect effects now and in the future. Predicted climate effects may prevent some populations from regaining self-sustaining status, despite local conservation actions. Our review revealed several knowledge gaps, notably a lack of clarity on the spatial extent of undisturbed habitat required for caribou populations to be stable. We used outcomes from our review to demonstrate how a mechanistic understanding of population decline can inform habitat-based conservation strategies for caribou. For populations residing within highly disturbed ranges, habitat restoration is a key recommendation of current conservation strategies, yet the large spatial extent of disturbances will require prioritization of areas for restoration. Maximizing the conservation return-on-investment for caribou will require a mechanistically informed prioritization process that targets conservation actions toward the primary mechanisms underlying population decline.