Fungal diseases pose significant threats to agriculture, impacting crop quality, productivity, and global food security. Succinate dehydrogenase Inhibitors (SDHIs) have played a pivotal role in the agrochemical industry due to their potent fungicidal activity, with widespread use for over 60 years. According to the Fungicide Resistance Action Committee (FRAC), the first SDHI was reported in 1966, and to date, 17 inhibitors have been approved and commercialized. This chapter provides a comprehensive overview of SDHIs, focusing on their classification, case studies, mechanism of action, role in disease control, structure–activity relationships (SAR), resistance mechanisms, synthetic approaches, and future challenges. It begins by defining and describing the structure of SDHIs and their critical roles in various metabolic pathways. It highlights case studies of fungal attacks on crops and their adverse effects on global crop yields. Fungal pathogens affect different plant parts—including roots, leaves, and fruits—leading to significant reductions in productivity. Novel SDHIs, particularly those incorporating carboxamide, nicotinamide, benzothiazole, and pyrazine-carboxamide-diphenyl-ether scaffolds, are essential in enhancing crop yields. However, resistance development due to genetic mutations in fungi and the environmental and health hazards associated with prolonged SDHI use remain significant challenges. Recent research emphasizes sustainable approaches to overcome these issues, aiming to improve the future application of SDHIs in agriculture.