The Organization for Economic Cooperation and Development's (OECD) Working Group for the Harmonization of Regulatory Oversight (Working Group) has taken the opportunity over the last several years to identify the challenges to environmental risk assessment of transgenic organisms, particularly plants. These initiatives have included most importantly, a report to the G8, the Rapporteur's Report from the OECD international symposium on LMOs and the Environment; and an internal workshop on Review of Consensus Documents and Future Work in Harmonization that emphasized priority setting. The outcome of these endeavors has informed the development of subsequent programs of work adopted by the Working Group. This paper identifies points raised at these conferences and meetings that relate to the science underpinning risk/safety assessment. Many of the points are similar over the timeframe of these endeavors and are still of current importance. The discussions at the OECD workshop on risk assessment held in Korea during the 9th International Symposium on the Biosafety of Genetically Modified Organisms will also influence the subsequent projects and priorities of the Working Group.