The evolution of herbicide resistant populations is a key issue in weed management and negatively affects the sustainability of a variety of annual and perennial cropping systems in southern Europe. This was determined by the excessive use of herbicides with specific biochemical targets and the lack of preventive cultural practices. In southern Europe different countries have similar trends in the evolution of herbicide resistance and its status in Greece, Italy, Portugal, Spain and Balkan countries is discussed. The introduction of conventionally-bred herbicide tolerant varieties is making the situation more complex. Easily accessible and frequently updated maps of resistance risk areas are helpful tools to document the status of resistance. There is a necessity to design cropping systems less dependent on herbicides. Weeds can no longer be regarded as a problem resolved by curative tactics, rather, integrated weed management should be a component of cropping systems design.