Drought is the main selection agent in Mediterranean ecosystems and it is been suggested as an important evolutionary force responsible for population diversification in these environments. However, population divergence in quantitative traits can be driven by either directional natural selection, genetic drift or both. To investigate the roles of these forces on among-population divergence in ecophysiological traits related to drought tolerance (Δ13C, SLA, leaf size, Nmass), we compared molecular and quantitative genetic differentiation among thirteen cork oak (Quercus suber L.) populations spanning over a gradient of rainfall and temperature. Population differentiation for height, specific leaf area and leaf nitrogen content far exceeded the molecular differentiation measured by six nuclear microsatellites and was associated with the climatic gradient in among-year rainfall variation. These results suggest (1) these traits are subjected to directional selection and (2) the genetic differences among populations are partly due to adaptation to the rainfall unpredictability at the place of origin. By contrast, the low among population divergence found in stem diameter, annual growth and carbon isotopic discrimination (a surrogate for water use efficiency) and the weak association with the environmental gradient suggest low or no directional selection on these traits under dry conditions. Among-population differentiation for neutral markers was not a good predictor for differentiation regarding the quantitative traits studied here, but for leaf size. The observed correlation between the genetic differentiation for leaf size and that for molecular markers was exclusively due to the association between leaf size and microsatellite QpZAG46, which suggests a possible linkage between microsatellite QpZAG46 and genes encoding for leaf size.