The long-term persistence of forest-dwelling caribou (Rangifer tarandus caribou) will probably be determined by management and conservation decisions. Understanding the evolutionary relationships between modern caribou herds, and how these relationships have changed through time will provide key information for the design of appropriate management strategies. To explore these relationships, we amplified microsatellite and mitochondrial markers from modern caribou from across the Southern Yukon, Canada, as well as mitochondrial DNA from Holocene specimens recovered from alpine ice patches in the same region. Our analyses identify a genetically distinct group of caribou composed of herds from the Southern Lakes region that may warrant special management consideration. We also identify a partial genetic replacement event occurring 1000 years before present, coincident with the deposition of the White River tephra and the Medieval Warm Period. These results suggest that, in the face of increasing anthropogenic pressures and climate variability, maintaining the ability of caribou herds to expand in numbers and range may be more important than protecting the survival of any individual, isolated sedentary forest-dwelling herd.