Abstract. The chemical features of 1,3,4-thiadiazoles were described in a numerous reviews focusing on the main approaches to the synthesis and modification. Simultaneously, thiadiazole scaffold was identified as the main structural component of approved drugs and biological agents with antimicrobial, antiviral, antitubercular, anti-inflammatory, anticonvulsant and analgetic activity. The significant biological activity of thiadiazole derivates promotes the scientists to further investigation of this heterocycle as a building block for medicinal chemistry. In this review, we discuss the efforts to identify new promising compounds based on aryl/heteryl substituted non-condensed thiadiazoles highliting the main approaches for the conjugation (hybridization) of heterocycles, derivatization and their pharmacological profile.