Understanding the ecological and evolutionary processes driving biodiversity patterns and allowing their persistence is of utmost importance. Many hypotheses have been proposed to explain spatial diversity patterns, including water‐energy availability, habitat heterogeneity, and historical climatic refugia. The main goal of this study is to identify if general spatial drivers of species diversity patterns of phylogenetic diversity (PD) and phylogenetic endemism (PE) at the global scale are also predictive of PD and PE at regional scales, using Iberian amphibians as a case study. Our main hypothesis assumes that topography along with contemporary and historical climate are drivers of phylogenetic diversity and endemism, but that the strength of these predictors may be weaker at the regional scale than it tends to be at the global scale. We mapped spatial patterns of Iberian amphibians' phylogenetic diversity and endemism, using previously published phylogenetic and distribution data. Furthermore, we compiled spatial data on topographic and climatic variables related to the water‐energy availability, topography, and historical climatic instability hypotheses. To test our hypotheses, we used Spatial Autoregressive Models and selected the best model to explain diversity patterns based on Akaike Information Criterion. Our results show that, out of the variables tested in our study, water‐energy availability and historical climate instability are the most important drivers of amphibian diversity in Iberia. However, as predicted, the strength of these predictors in our case study is weaker than it tends to be at global scales. Thus, additional drivers should also be investigated and we suggest caution when interpreting these predictors as surrogates for different components of diversity.