Among Chalcogen elements, sulfur, selenium, and tellurium, occupy a central position in both nature and synthetic chemistry. Their unique electronic structures give rise to diverse bonding patterns and reactivity, making them indispensable in biological systems and highly attractive in molecular design. Sulfur, for example, is a fundamental component of amino acids, cofactors, and signaling molecules, while selenium plays critical roles in antioxidant enzymes and redox regulation. Tellurium, although less common in biology, has recently emerged as a promising element for creating molecules with distinctive pharmacological and physicochemical profiles. These intrinsic properties explain why chalcogen chemistry has become an increasingly powerful tool for medicinal chemists seeking innovative solutions. In this way, incorporating chalcogen elements into organic frameworks has emerged as a versatile approach for generating novel compounds with significant potential in medicine and materials science. This presentation will highlight our recent efforts on the synthesis of selenium-, sulfur- and tellurium-functionalized molecules as a powerful tool in drug discovery. Recent advances in sustainable synthetic methodologies have made the incorporation of chalcogen atoms more accessible, enabling the design of innovative molecular scaffolds with therapeutic relevance. By showcasing representative examples and future perspectives, I aim to illustrate how chalcogen chemistry can expand the medicinal chemist’s toolbox and inspire the development of next-generation drugs.