Sulfur-containing scaffolds are crucial in pharmaceuticals, with over 362 FDA-approved drugs containing sulfur (excluding oxygen and nitrogen). Common scaffolds include sulfonamides, thioethers, sulfones, and penicillins. Sulfonamides, first used as antibiotics, are widely used in various drugs, such as cyclothiazide. Recent advances in their synthesis include water-based methods and flow chemistry, which improve efficiency and sustainability. Sulfonamides can also be synthesized via copper-catalyzed oxidative coupling and iodine-mediated reactions. Sulfur dioxide fixation is a promising method for sulfonamide synthesis, with DABSO as a stable sulfur source. Thioethers, present in 8.8% of sulfur-containing drugs, include compounds like cimetidine. Their synthesis often involves Pd-catalyzed cross-coupling reactions. Recent methods include Cu-catalyzed protocols and sulfur dioxide-mediated reactions. Sulfones are found in many drugs and are synthesized via oxidation of sulfides. Recent methods include palladium-catalyzed reactions using DABSO. Penicillins, containing sulfur, are important antibiotics. Their synthesis involves biosynthesis and chemical methods, with recent advances in radical cyclization and transition metal-catalyzed processes. The review highlights the importance of sulfur-containing scaffolds in drug development, emphasizing the need for more general and efficient synthetic methods. Various sulfur-containing moieties, such as thiophenes and thiazoles, are also present in pharmaceuticals. Despite advancements, challenges remain in the synthesis of sulfur-containing drugs, requiring further research and development.Sulfur-containing scaffolds are crucial in pharmaceuticals, with over 362 FDA-approved drugs containing sulfur (excluding oxygen and nitrogen). Common scaffolds include sulfonamides, thioethers, sulfones, and penicillins. Sulfonamides, first used as antibiotics, are widely used in various drugs, such as cyclothiazide. Recent advances in their synthesis include water-based methods and flow chemistry, which improve efficiency and sustainability. Sulfonamides can also be synthesized via copper-catalyzed oxidative coupling and iodine-mediated reactions. Sulfur dioxide fixation is a promising method for sulfonamide synthesis, with DABSO as a stable sulfur source. Thioethers, present in 8.8% of sulfur-containing drugs, include compounds like cimetidine. Their synthesis often involves Pd-catalyzed cross-coupling reactions. Recent methods include Cu-catalyzed protocols and sulfur dioxide-mediated reactions. Sulfones are found in many drugs and are synthesized via oxidation of sulfides. Recent methods include palladium-catalyzed reactions using DABSO. Penicillins, containing sulfur, are important antibiotics. Their synthesis involves biosynthesis and chemical methods, with recent advances in radical cyclization and transition metal-catalyzed processes. The review highlights the importance of sulfur-containing scaffolds in drug development, emphasizing the need for more general and efficient synthetic methods. Various sulfur-containing moieties, such as thiophenes and thiazoles, are also present in pharmaceuticals. Despite advancements, challenges remain in the synthesis of sulfur-containing drugs, requiring further research and development.