The potential for using genetic modification (GM) to enhance the nutritional composition of crops (for either direct human consumption or as animal feed) has been recognized since the dawn of the GM era, with such ‘output’ traits being considered as distinct, if not potentially superior, to ‘input’ traits such as herbicide tolerance and insect resistance. However, while input traits have successfully been used and now form the basis of GM agriculture, output trait GM crops are still lagging behind after 20 years. This is despite the demonstrable benefits that some nutritionally enhanced crops would bring and the proven value of GM technologies. This Review considers the present state of nutritional enhancement through GM, highlighting two high-profile examples of nutritional enhancement—Golden Rice and omega-3 fish oil crops—systematically evaluating the progress, problems and pitfalls associated with the development of these traits. This includes not just the underlying metabolic engineering, but also the requirements to demonstrate efficacy and field performance of the crops and consideration of regulatory, intellectual property and consumer acceptance issues.