The regulation of genetic engineering varies widely by country. Countries such as the United States, Canada, Lebanon and Egypt use substantial equivalence as the starting point when assessing safety, while many countries such as those in the European Union, Brazil and China authorize GMO cultivation on a case-by-case basis. Many countries allow the import of GM food with authorization, but either do not allow its cultivation (Russia, Norway, Israel) or have provisions for cultivation, but no GM products are yet produced (Japan, South Korea). Most countries that do not allow for GMO cultivation do permit research. Most (85%) of the world's GMO crops are grown in the Americas (North and South). One of the key issues concerning regulators is whether GM products should be labeled. Labeling of GMO products in the marketplace is required in 64 countries. Labeling can be mandatory up to a threshold GM content level (which varies between countries) or voluntary. A study investigating voluntary labeling in South Africa found that 31% of products labeled as GMO-free had a GM content above 1.0%. In Canada and the US labeling of GM food is voluntary, while in Europe all food (including processed food) or feed which contains greater than 0.9% of approved GMOs must be labelled.

There is a scientific consensus that currently available food derived from GM crops poses no greater risk to human health than conventional food, but that each GM food needs to be tested on a case-by-case basis before introduction. Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe. The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation.

There is no evidence to support the idea that the consumption of approved GM food has a detrimental effect on human health. Some scientists and advocacy groups, such as Greenpeace and World Wildlife Fund, have however called for additional and more rigorous testing for GM food.

The development of a regulatory framework concerning genetic engineering began in 1975, at Asilomar, California. The first use of Recombinant DNA (rDNA) technology had just been successfully accomplished by Stanley Cohen and Herbert Boyer two years previously and the scientific community recognized that as well as benefits this technology could also pose some risks. The Asilomar meeting recommended a set of guidelines regarding the cautious use of recombinant technology and any products resulting from that technology. The Asilomar recommendations were voluntary, but in 1976 the US National Institute of Health (NIH) formed a rDNA advisory committee. This was followed by other regulatory offices (the United States Department of Agriculture (USDA), Environmental Protection Agency (EPA) and Food and Drug Administration (FDA)), effectively making all rDNA research tightly regulated in the US.

In 1982 the Organisation for Economic Co-operation and Development (OECD) released a report into the potential hazards of releasing genetically modified organisms (GMOs) into the environment as the first transgenic plants were being developed. As the technology improved and genetically organisms moved from model organisms to potential commercial products the US established a committee at the Office of Science and Technology (OSTP) to develop mechanisms to regulate the developing technology. In 1986 the OSTP assigned regulatory approval of genetically modified plants in the US to the USDA, FDA and EPA.

The basic concepts for the safety assessment of foods derived from GMOs have been developed in close collaboration under the auspices of the OECD, the World Health Organization (WHO) and Food and Agriculture Organization (FAO). A first joint FAO/WHO consultation in 1990 resulted in the publication of the report ‘Strategies for Assessing the Safety of Foods Produced by Biotechnology’ in 1991. Building on that, an international consensus was reached by the OECD's Group of National Experts on Safety in Biotechnology, for assessing biotechnology in general, including field testing GM crops. That Group met again in Bergen, Norway in 1992 and reached consensus on principles for evaluating the safety of GM food; its report, ‘The safety evaluation of foods derived by modern technology – concepts and principles’ was published in 1993. That report recommends conducting the safety assessment of a GM food on a case-by-case basis through comparison to an existing food with a long history of safe use. This basic concept has been refined in subsequent workshops and consultations organized by the OECD, WHO, and FAO, and the OECD in particular has taken the lead in acquiring data and developing standards for conventional foods to be used in assessing substantial equivalence.

The Cartagena Protocol on Biosafety was adopted on 29 January 2000 and entered into force on 11 September 2003. It is an international treaty that governs the transfer, handling, and use of genetically modified (GM) organisms. It is focused on movement of GMOs between countries and has been called a de facto trade agreement. One hundred and seventy-two countries are members of the Protocol and many use it as a reference point for their own regulations. Also in 2003 the Codex Alimentarius Commission of the FAO/WHO adopted a set of "Principles and Guidelines on foods derived from biotechnology" to help countries coordinate and standardize regulation of GM food to help ensure public safety and facilitate international trade. and updated its guidelines for import and export of food in 2004,

The European Union first introduced laws requiring GMOs to be labelled in 1997. In 2013, Connecticut became the first state to enact a labeling law in the US, although it would not take effect until other states followed suit.