This review of the safety assessment of genetically modified (GM) crops is focused primarily on the process and progress in the United States (US). It reviews the development of the safety evaluation process from the Asilomar conference in 1975 considering issues relevant to recombinant DNA technology,to discussions between the US government,academic and industrial scientists between 1984 and 1994 when the first GM crops were being field tested and evaluated commercial release for food and feed production. International guidelines were also reviewed for consistency with the US system. The overall process includes consideration of information relating to history of safe or unsafe human and exposure to the gene source and expressed proteins. The primary considerations of safety for dietary proteins are whether or not some consumers are sensitized and have IgE antibodies against the protein encoded by the transgene or whether the transgene represents a risk of eliciting celiac disease. The process considers potential toxic effects of expressed proteins as well as potential impacts on human and animal nutrition. The process in the US is consistent with Codex Alimentarius recommendations. It follows a science based process based on justifiable hypotheses. To date there is no evidence that GM crops approved in the US have harmed human or animal consumers. The evaluation takes into account genetic and environmental variation in products produced by plant varieties and is intended to maintain the standard that foods developed from GM plants are intended to be as safe as non-GM genetically similar varieties.