The PROTAC (PROteolysis TArgeting Chimera) technology is a method of targeting intracellular proteins previously considered undruggable. This technology utilizes the ubiquitin—proteasome system in cells to specifically degrade target proteins, thereby offering significant advantages over conventional small-molecule inhibitors of the enzymatic func- tion. Preclinical and preliminary clinical trials of PROTAC-based compounds (degraders) are presented. The review considers the general principles of the design of degraders. Advances and challenges of the PROTAC technology are discussed.