Septoria tritici blotch (STB), caused by fungal agent Zymoseptoria tritici (previously known as Mycosphaerella graminicola) is a devastative foliar wheat diseases globally. Importance and potential threat of STB have been discussed historically and geographically. This paper reviews information on the Z. tritici—wheat pathosystem and proposes approaches to identify resistance genes and to advance in breeding for STB resistance. Screening of resistant lines/cultivars, QTL mapping analysis within genetic populations derived from crosses, detection of new resistance gene(s) and finally application of Stb gene carrier line/cultivar in crosses are the major stages of a practical wheat-breeding program against STB of wheat. Phenotyping and genotyping outputs on the top of each other should confirm each other, so it needs to expose a resistance gene carrier line/cultivar in the epidemic condition at seedling/adult plant stage to confirm resistance performance of detected gene(s) in the real condition. On the other word, detecting an associated QTL to resistance should not be considered as the end of investigation. Climate change resulted geographical disease pattern conversion where some diseases became more important in some area where they had not been serious in the past and vice versa. Hence, a reconsideration of wheat disease importance zone is necessary to predict regions where STB is and will be a limitation for wheat yield improvement.