| Summary: | Coffee (<i>Coffea</i> spp.) is an economically important crop widely cultivated in (sub) tropical countries worldwide. Commercial coffee production relies mainly on two related species, namely <i>C. arabica</i> and <i>C. canephora</i>. Due to their perennial growth habit, cultivation practices, and narrow genetic diversity, coffees are constantly exposed to many diseases and pests. Coffee leaf rust (<i>Hemileia vastatrix</i> Berk. et Br.), coffee berry disease (<i>Colletotrichum kahawae</i> Bridge and Waller), and coffee wilt disease (<i>Gibberella xylarioides</i> Heim and Saccas/<i>Fusarium xylarioides</i>) are the top fungal diseases affecting <i>C. arabica</i> and <i>C. canephora</i> production areas worldwide. In many regions, chemical-based control measures are widely used and are the only way to control the diseases. Developing resistant cultivars is one of the prerequisites for increasing sustainable market demand and agriculture. However, desired and required resistance traits are not always available in the gene pool. Furthermore, from other crops it is clear that dominant resistance genes introduced into varieties are not durable because of pathogen variability and the emergence of new races of the different pathogens. Utilization of altered susceptibility genes (<i>S</i> genes) offers a novel and alternative strategy for the breeding of durable and broad-spectrum resistance. The <i>S</i> gene encodes a host factor that facilitates a compatible interaction with the pathogen, and impairment of <i>S</i> genes leads to loss-of-susceptibility. In this review, guidelines for effective identification, characterization, and utilization of dysfunctional <i>S</i> genes are proposed to aid breeding activities in order to introduce durable resistance in <i>Coffea</i> spp. Several candidate <i>S</i> genes likely contributing to the susceptibility of <i>Colletotrichum</i> spp., <i>Fusarium</i> spp., and <i>Meloidogyne</i> spp. are discussed. With the rapid development of genetic engineering techniques, including CRISPR-associated systems, we now have the potential to accelerate the application of <i>S</i> genes to achieve durable resistance in coffee.
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