Genetically modified (GM) crops have generated a great deal of controversy. Since commercially introduced to farmers in 1996, the global area cultivated with GM crops has increased 94-fold. The rapid adoption of GM technology has had substantial socio-economic impacts which a vast amount of technical and non-technical literature has addressed in the last two decades. However, contradictory results between individual studies abound. Extensive and transparent reviews concerning this contentious and complex issue could help promote evidence-based dialogue among the diverse parties involved. This protocol specifies the methodology for identifying, evaluating, and mapping evidence related to the main review question: what are the socio-economic impacts of genetically modified crops worldwide? This question has been subdivided into the following topics: (a) farm-level impacts; (b) impacts of coexistence regulations; (c) impacts along the supply chain; (d) consumer-level impacts; (e) impacts on food security; and (f) environmental economic impacts. The search strategy includes the identification of primary studies from general scientific databases; global, regional, and national specialist databases; an on-line search engine; institutional websites; journal websites; subject experts/researchers; and serendipity. Searches will be conducted in six languages (Chinese, English, French, German, Portuguese, and Spanish). Identified studies will be screened for inclusion/exclusion criteria by a group of multi-language reviewers. Finally, pre-defined data from the studies will be extracted, mapped, and presented in a report. Potential research gaps will be identified and discussed, and the review process will be documented in an open-access database (i.e. CADIMA, http://www.cadima.info/).