The article reviews the synthesis and application of sulfur-containing scaffolds in pharmaceuticals, focusing on sulfonamides, thioethers, sulfones, and penicillins. Sulfur-derived functional groups are prevalent in a wide range of pharmaceuticals and natural products, with sulfur being the third most common heteroatom in FDA-approved drugs. The review highlights the historical significance of sulfonamides, which were the first systemic antibiotics and have since been used for various therapeutic purposes. Recent advances in the synthesis of these scaffolds, including environmentally friendly methods and the use of sulfur dioxide fixation, are discussed. The article also covers the synthesis of thioethers, sulfones, and penicillins, detailing various catalytic and non-catalytic approaches. The challenges and future directions in the development of more general methods for synthesizing sulfur-containing pharmaceutical molecules are also addressed.The article reviews the synthesis and application of sulfur-containing scaffolds in pharmaceuticals, focusing on sulfonamides, thioethers, sulfones, and penicillins. Sulfur-derived functional groups are prevalent in a wide range of pharmaceuticals and natural products, with sulfur being the third most common heteroatom in FDA-approved drugs. The review highlights the historical significance of sulfonamides, which were the first systemic antibiotics and have since been used for various therapeutic purposes. Recent advances in the synthesis of these scaffolds, including environmentally friendly methods and the use of sulfur dioxide fixation, are discussed. The article also covers the synthesis of thioethers, sulfones, and penicillins, detailing various catalytic and non-catalytic approaches. The challenges and future directions in the development of more general methods for synthesizing sulfur-containing pharmaceutical molecules are also addressed.