In some respects genetically modified organisms (GMOs) can no longer be considered a novelty in plant breeding. In some countries the larger part of the production of specific crops is in fact GMO production. Examples are the production of soya bean and maize in the USA. In general, these crops have incorporated genes that code for resistance to either herbicide or insects, or both. There are, however, other interesting developments, both with relation to the techniques used to create GMOs as well as to the introduced traits. This review provides an overview of recent developments in the broad area of biotechnology. Furthermore, regulatory aspects are discussed in a global perspective, with a focus on the situation in the European Union. In general, the basic approach to the food and feed safety assessment of GMOs is the same in different parts of the world; there may, however, be differences in the detailed procedures as applied in different countries. The general aspects of the safety assessment strategies are described and explained. Also, an overview is provided on research developments in the area of the food and feed safety assessment strategies, especially on the application of the so-called ‘omics’-technologies (transcriptomics, proteomics, and metabolomics) as a non-targeted approach in the comparative safety assessment of GMOs. It is concluded that it may in the future be necessary to adapt current national and international guidelines for the food and feed safety assessment of GMOs to accommodate the products of these novel developments having the potential to produce much more profound changes in the metabolism of crop plants than in today’s GMOs.