The research involved the application of CORINE Land Cover categories in order to analyse changes in land cover and in the socio-economic system over the last 50 years in Molise (Southern Italy). The boundaries of the study area corresponded to those of six local councils: Guglionesi, Montecilfone, Montenero di Bisaccia, Petacciato, San Giacomo degli Schiavoni and Termoli. It is an area which has undergone a great anthropic agricultural impact after the II World War, but, however, still has natural settings worth preserving, as can be seen by the presence of seven Sites of Community Interest (sensu “Habitat Directive” 92/43/EC). For the analyses of the land cover changes, geo-databases were consulted or specially constructed. The aerial photographs from GAI 1954-55 flight, appropriately georectified, and the aerial photograph ITA2000 and AGEA 2004 flights were adopted to draw up the land use/cover maps at a scale of 1.10.000.The study of vegetation was performed using the phytosociological method. In brief, the results show that the landscape of the study area has become more fragmented due mostly to effects of continuous human disturbances and agricultural improvement during the study period. Overall, the landscape is today characterised by the predominance of agricultural use and the sparse colonization of the natural vegetation, mainly by linear vegetational formations (mainly riparian woods).