Effective conservation of crop wild relative (CWR) species is essential for the sustainable use and genetic improvement of crop varieties, which offers greater opportunities for world food security, particularly in modern agroecosystems where CWR diversity is under severe threat. Factors such as habitat fragmentation, human disturbances, global climate change, and invasion of harmful alien species have been identified to be responsible for losses and threats to CWR diversity. However, a neglected factor, gene introgression from domesticated species through repeated outcrossing, may have a significant impact on CWR diversity. Introgression can influence genetic diversity and evolutionary processes of CWR populations through effects such as demographic swarming, genetic assimilation, and selective sweep. When largely enhancing or reducing fitness of wild plants, the introgression of crop genes will impose more significant genetic and evolutionary impacts on CWR populations, leading to undesired consequences for conserved CWR populations and species. This situation is particularly true when genetically engineered (GE) crops are deployed for commercial cultivation. It is argued that a GE crop usually contains transgenes with strong natural selection advantages, and such transgenes introgressed into CWR populations may have strong impacts on their genetic diversity and evolutionary processes, threatening their conservation. This article reviews the challenge of crop-wild gene flow, and particularly transgene introgression from GE crops, for the in situ conservation of wild relative species. The design of effective management strategies for conserving CWR species under the scenario of extensive cultivation of GE crops is also discussed.