For the implementation of the Framework Council Directive 91/414/EEC, participation of all member states (MS) is required. In the first round of the review program of plant protection products, Mediterranean countries have successfully performed their proportional work share for the central registration of the active substances and the national registration of the respective plant protection products. However, some issues of risk assessment, related to appropriate estimation of exposure, still require further refinement and adaptation to the Mediterranean conditions. Issues related to the estimation of agricultural worker exposure to plant protection products due to different agronomic practices and conditions, identified shortcomings in the consumer risk assessment related to different habits of the Mediterranean population and different needs of Mediterranean agriculture will be discussed. Finally, the possible effects of the Directive 91/414/EEC upon the plant protection of Mediterranean countries, due to the withdrawal from the market of a wide range of plant protection products is also a parameter that has to be considered.