Alternatives to protect crops against diseases are desperately needed to secure world food production and make agriculture more sustainable. Genetic resistance to pathogens utilized so far is mostly based on single dominant resistance genes that mediate specific recognition of invaders and that is often rapidly broken by pathogen variants. Perturbation of plant susceptibility (S) genes offers an alternative providing plants with recessive resistance that is proposed to be more durable. S genes enable the establishment of plant disease, and their inactivation provides opportunities for resistance breeding of crops. However, loss of S gene function can have pleiotropic effects. Developments in genome editing technology promise to provide powerful methods to precisely interfere with crop S gene functions and reduce tradeoffs.