The problem of unintended effects, which may be caused by genetic modification of plants, is analyzed. The factors that provoke the occurrence of unintended effects in genetically engineered plants, the consequences caused by the influence of these factors, and the possibility to minimize such effects by the use of improved methods of genetic engineering are discussed. Modern methodological approaches that can be applied to the analysis of unintended effects considered as a stage of safety assessment of transgenic plants, especially the methods of molecular profiling with the use of different “-omic” technologies, are described.