Protein ubiquitination is a highly conserved post-translational modification through which cells initiate the proteasomal degradation of undesired, aberrant, or damaged proteins. Protein ubiquitination plays a crucial role in protein homeostasis and regulates a wide range of essential physiological processes including DNA repair, immunological response, cell survival and apoptosis. Dysregulation of ubiquitination is associated with various pathologies including cancers, neurodegenerative diseases, and immune disorders. The ubiquitin-proteasome system (UPS) machinery has been utilized in therapeutic research as it can be manipulated to induce the degradation of undruggable proteins in a superior manner to traditional drug modalities. One such a method of specific protein degradation is the use of heterobifunctional molecules such as proteolysis targeting chimeras (PROTACs). This literature review will focus on the composition, mechanism of action and developmental milestones of PROTACs, comparing these against traditional drug discovery and treatment approaches. In addition, the potential benefits of PROTAC usage will be highlighted by analyzing their practical applications in drug therapies.