Proteolysis targeting chimeras (PROTACs) have become a leading technology in targeted protein degradation. These molecules consist of three moieties: a protein of interest (POI) ligand and an E3 ligase ligand tethered by a linker. PROTACs induce proximity between the POI and the E3 ligase, thereby resulting in efficient ubiquitin transfer and polyubiquitination of the target protein. This ubiquitination then serves as recognition for the proteasome and the polyubiquitinated protein is subsequently degraded by the proteasome. Therefore, PROTACs act as catalysts and can participate in successive ternary complex formations. This approach offers various advantages over traditional occupancy-driven therapeutic modalities. While occupancy-driven approaches need extensive optimization of the ligand to ensure adequate physiological effects, PROTACs often do not need high affinity towards their POI due to the catalytic mode of action. Additionally, the POI ligand moiety of PROTACs does not necessarily have to bind to an active site of a protein. The POI can be targeted at any pocket addressable by a small molecule ligand, thereby reducing the competition with endogenous ligands, which usually necessitates high affinity of the ligands to the target protein. With the first PROTACs entering late-stage clinical trials, there is growing interest in the exploration of new methodologies to expand the toolkit for targeted protein degradation. To broaden the scope of targeted protein degradation, innovative approaches such as molecular glues, lysosome targeting chimeras (LYTACs), autophagy targeting chimeras (AUTACs), and antibody targeted chimeras (AbTACs) have emerged as promising strategies. While these novel methods, have expanded the range of proteins that can be targeted, they have limitations in terms of spatial and temporal control of their activity. Once administered, these degraders typically act continuously, degrading target proteins regardless of their physiological context or location, which can lead to unwanted toxicity. Despite their versatility, the lack of precise modulation of protein function remains a challenge for therapeutic applications.