AbstractMotivationMore than half of Earth's species are contained in a mere 1.4% of its land area, but the climates of many of these biodiversity hotspots are projected to disappear as a consequence of anthropogenic climate change. There is growing recognition that spatio‐temporal patterns of climate in biodiversity hotspots have shaped biological diversity over a variety of historical time‐scales, yet these patterns are rarely taken into account in assessments of the vulnerability of biodiversity hotspots to future climate change. In our review, we synthesize the climatic processes that have led to the diversification of hotspots and interpret what this means in the context of anthropogenic climate change. We demonstrate the importance of mesoclimatic processes and fine‐scale topographical heterogeneity, in combination with climatic variability, in driving speciation processes and maintaining high levels of diversity. We outline why these features of hotspots are crucial to understanding the impacts of anthropogenic climate change and discuss how recent advances in predictive modelling enable vulnerability to be understood better.LocationGlobal.Main conclusionsWe contend that many, although not all, biodiversity hotspots have climate and landscape characteristics that create fine‐scale spatial variability in climate, which potentially buffers them from climatic changes. Temporally, many hotspots have also experienced stable climates through evolutionary time, making them particularly vulnerable to future changes. Others have experienced more variable climates, which is likely to provide resilience to future changes. Thus, in order to identify risk for global biodiversity, we need to consider carefully the influence of spatio‐temporal variability in climate. However, most vulnerability assessments in biodiversity hotspots are still reliant on climate data with coarse spatial and temporal resolution. Higher‐resolution forecasts that account for spatio‐temporal variability in climate and account better for the physiological responses of organisms to this variability are much needed to inform future conservation strategies.