Crop diseases are major factors responsible for substantial yield losses worldwide,which affects global food security.The use of resistance (R) genes is an effective and sustainable approach to controlling crop diseases.Here,we review recent advances on R gene studies in the major crops and related wild species.Current understanding of the molecular mechanisms underlying R gene activation and signaling,and susceptibility (S) gene-mediated resistance in crops are summarized and discussed.Furthermore,we propose some new strategies for R gene discovery,how to balance resistance and yield,and how to generate crops with broad-spectrum disease resistance.With the rapid development of new genome-editing technologies and the availability of increasing crop genome sequences,the goal of breeding next-generation crops with durable resistance to pathogens is achievable,and will be a key step toward increasing crop production in a sustainable way.