The International Life Sciences Institute Health and Environmental Sciences Institute Protein Allergenicity Technical Committee hosted an international workshop November 16-17, 2009, in Paris, France, with over 60 participants from academia, government, and industry to review and discuss the potential utility of "-omics" technologies for assessing the variability in plant gene, protein, and metabolite expression. The goal of the workshop was to illustrate how a plant's constituent makeup and phenotypic processes can be surveyed analytically. Presentations on the "-omics" techniques (i.e., genomics, proteomics, and metabolomics) highlighted the workshop, and summaries of these presentations are published separately in this supplemental issue. This paper summarizes key messages, as well as the consensus points reached, in a roundtable discussion on eight specific questions posed during the final session of the workshop. The workshop established some common, though not unique, challenges for all "-omics" techniques, and include (a) standardization of separation/extraction and analytical techniques; (b) difficulty in associating environmental impacts (e.g., planting, soil texture, location, climate, stress) with potential alterations in plants at genomic, proteomic, and metabolomic levels; (c) many independent analytical measurements, but few replicates/subjects--poorly defined accuracy and precision; and (d) bias--a lack of hypothesis-driven science. Information on natural plant variation is critical in establishing the utility of new technologies due to the variability in specific analytes that may result from genetic differences (crop genotype), different crop management practices (conventional high input, low input, organic), interaction between genotype and environment, and the use of different breeding methods. For example, variations of several classes of proteins were reported among different soybean, rice, or wheat varieties or varieties grown at different locations. Data on the variability of allergenic proteins are important in defining the risk of potential allergenicity. Once established as a standardized assay, survey approaches such as the "-omics" techniques can be considered in a hypothesis-driven analysis of plants, such as determining unintended effects in genetically modified (GM) crops. However, the analysis should include both the GM and control varieties that have the same breeding history and exposure to the same environmental conditions. Importantly, the biological relevance and safety significance of changes in "-omic" data are still unknown. Furthermore, the current compositional assessment for evaluating the substantial equivalence of GM crops is robust, comprehensive, and a good tool for food safety assessments. The overall consensus of the workshop participants was that many "-omics" techniques are extremely useful in the discovery and research phases of biotechnology, and are valuable for hypothesis generation. However, there are many methodological shortcomings identified with "-omics" approaches, a paucity of reference materials, and a lack of focused strategy for their use that currently make them not conducive for the safety assessment of GM crops.