We investigate whether the observed surface specific humidity (q) trends over the Mediterranean region in the period 1974–2003 are consistent with climate model (CMIP3, CMIP5) simulations of q in response to anthropogenic forcing (Greenhouse gas and sulphate aerosols). The natural (internal) variability is estimated using 6,000-year of pre-industrial control simulations. With the exception of winter, the increases in annual and seasonal q over this region are very unlikely (with less than 1%chance) due to natural (internal) variability or natural forcing alone. Using several climate models and ensemble means, we demonstrate that the large-scale component (spatial-mean trend) of the anthropogenic forcing is detectable (at 1% level) in the annual and seasonal trends of q (except winter). However, the smaller-scale component (spatial anomalies about the mean trend) of the anthropogenic signal is detectable only in warm seasons (spring and summer). We further show that the spread of projected trends based on the A1B scenario derived from 13 CMIP3 models encompasses the observed area-averaged trend in q. This may imply that the observed trends of surface humidity, which is an important factor in human thermal comfort, serves as an illustration of plausible future expected change in the region.