The chemical understanding of biological processes provides not only a deeper insight but also a solution to abnormal biological functioning. Protein degradation, a natural biological process for debris removal in the cell, has been studied for years. The recent finding that natural degradation pathways can be utilized for therapeutic purposes is a paradigm shift in the drug discovery approach. Methods such as Proteolysis Targeting Chimera (PROTAC), lysosomal targeting chimera, hydrophobic tagging, AUtophagy TArgeting Chimera, AUTOphagy TArgeting Chimera and several other variants of these methods have made a considerable impact on the way of drug design. Few selected examples testify that a huge wave of change is on the way. The drug design based on the targeted protein degradation is a powerful tool in our arsenal. More molecules will be invented that will uncover the hidden secrets of biological functioning and provide enduring solutions to several unmet medical needs.