In chemical synthesis, the uses of solvents are inevitable, and it has been a practice since the inception of the process. With time it gets into the notice that most of the essential solvents have a great potential to cause acute health hazards, which include health-related complications as severe. There was a continuous urge to getting some solution to overcome this problem without compromising the quality of the synthesis process. Kamlet Taft parameter (K-T) is such a tool that can provide detailed information about the solvent characteristics related to the synthesis process thus enabling the selection of the solvent with a lower hazardous index compared with the high one. It has also contributed significantly to tackle environmental hazards by replacing the hazardous dipolar solvent in synthetic chemistry. A solvent pair mixture-Hydrogen bond donor and Hydrogen bond acceptor-is used to replace the routine hazardous solvents. This review aimed at the systematic highlight of the K-T parameters, which will be useful for the selection of suitable solvents for different chemical synthesis, specifically giving importance to drug synthesis. The review will provide insight into the different applications of K-T parameters to ease the comparison of these applications. It will also guide to estimate the solvent effects in synthesis, crystallization, and formulations of pharmaceuticals and biopharmaceuticals with systematic classification, analysis, and comparison of the reported work.