Safety assessment of novel proteins in genetic-engineered foods is a key component of the overall safety evaluation for these products. Since allergens are typically proteins, assessment of the potential allergenicity of the novel proteins in genetically engineered foods is critical. This article reviews methods available to assess the potential allergenicity of novel proteins, as well as problems and deficiencies in the existing methods. The role of bioinformatics and knowledge of allergenic epitopes in developing new approaches to this problem is discussed.