Andean plant species are predicted to shift their distributions, or ‘migrate,’ upslope in response to future warming. The impacts of these shifts on species' population sizes and their abilities to persist in the face of climate change will depend on many factors including the distribution of individuals within species' ranges, the ability of species to migrate and remain at equilibrium with climate, and patterns of human land-use. Human land-use may be especially important in the Andes where anthropogenic activities above tree line may create a hard barrier to upward migrations, imperiling high-elevation Andean biodiversity. In order to better understand how climate change may impact the Andean biodiversity hotspot, we predict the distributional responses of hundreds of plant species to changes in temperature incorporating population density distributions, migration rates, and patterns of human land-use. We show that plant species from high Andean forests may increase their population sizes if able to migrate onto the expansive land areas above current tree line. However, if the pace of climate change exceeds species' abilities to migrate, all species will experience large population losses and consequently may face high risk of extinction. Using intermediate migration rates consistent with those observed for the region, most species are still predicted to experience population declines. Under a business-as-usual land-use scenario, we find that all species will experience large population losses regardless of migration rate. The effect of human land-use is most pronounced for high-elevation species that switch from predicted increases in population sizes to predicted decreases. The overriding influence of land-use on the predicted responses of Andean species to climate change can be viewed as encouraging since there is still time to initiate conservation programs that limit disturbances and/or facilitate the upward migration and persistence of Andean plant species.