A rapidly expanding toolbox of techniques available for genome editing provides the basis for a new continuum in types of modifications that can be introduced into a genome and blur the bimodal GMO vs. non-GMO (genetically modified organism) divide. Site-directed nucleases (SDN) are now used to modify existing nucleotides within genomes instead of adding recombined DNA as transgenes. Moreover, new gene drive approaches are in development based on SDNs. A number of potential drive applications have been reported, but uncertainties in trait stability and limitations in knowledge of the affected system at various temporal and spatial levels slow down their current uses. Adoption of new genome targeted technology takes place in a social context. The context will vary between countries and cultures, expressed in values, ethics, politics and priorities — that are translated into different regulatory approaches. Some developed products using new genome editing techniques clearly fall under internationally negotiated regulations of GMOs. However, other product outcomes of editing techniques challenge our current understanding and definition of GMOs. There is an urgent need for further research, for building international consensus and harmonizing regulatory approaches to facilitate categorization, predictability, transparency, trust and trade.