Wheat productivity is threatened by global climate change. In several parts of NW Europe it will get warmer and dryer during the main crop growing period. The resulting likely lower realized on-farm crop yields must be kept by breeding for resistance against already existing and emerging diseases among other measures. Multi-disease resistance will get especially crucial. In this review, we focus on disease resistance breeding approaches in wheat, especially related to rust diseases and Fusarium head blight, because simulation studies of potential future disease risk have shown that these diseases will be increasingly relevant in the future. The long-term changes in disease occurrence must inevitably lead to adjustments of future resistance breeding strategies, whereby stability and durability of disease resistance under heat and water stress will be important in the future. In general, it would be important to focus on non-temperature sensitive resistance genes/QTLs. To conclude, research on the effects of heat and drought stress on disease resistance reactions must be given special attention in the future.